HYPERTENSION
(HIGH BLOOD PRESSURE)
(Page 2)

Ogihara T, Hiwada K, Matsuoka H, Matsumoto M, Shimamoto K, Ouchi Y, Abe I, Fujishima M, Morimoto S, Nakahashi T, Mikami H, Kohara K, Takasaki M, Takizawa S, Kiyohara Y, Ibayashi S, Eto M, Ishimitsu T, Nakamura T, Masusa A, Takagawa Y
Department of Geriatric Medicine, Osaka University Medical School.
Nippon Ronen Igakkai Zasshi 1996 Dec;33(12):945-75

We propose the following guidelines for treatment of hypertension in the elderly. 1. Indications for Treatment.

1) Age: Lifestyle modification is recommended for patients aged 85 years and older. Antihypertensive therapy should be limited to patients in whom the merit of the treatment is obvious.

2) Blood pressure: Systolic BP > 160 mmHg, diastolic BP > 90 approximately 10 mmHg. Systolic BP < age + 100 mmHg for those aged 70 years and older. Patients with mild hypertension (140-160/ 90-95 mmHg) associated with cardiovascular disease should be considered for antihypertensive drug therapy.

2. Goal of Therapy for BP: The goal BP in elderly patients is higher than that in younger patients (BP reduction of 10-20 mmHg for systolic BP and 5-10 mmHg for diastolic BP). In general, 140-160/< 90 mmHg is recommended as the goal. However, lowering the BP below 150/85 should be done with caution.

3. Rate of Lowering BP: Start with half the usual dose, observe at the same dose for at least four weeks, and reach the target BP over two months. Increasing the dose of antihypertensive drugs should be done very slowly. 4. Lifestyle Modification:

1) Dietary modification:

(1) Reduction of sodium intake is highly effective in elderly patients due to their high salt-sensitivity. NaCl intake of less than 10 g/day is recommended. Serum Na+ should be occasionally measured.

(2) Potassium supplementation is recommended, but with caution in patients with renal insufficiency.

(3) Sufficient intake of calcium and magnesium is recommended.

(4) Reduce saturated fatty acids. Intake of fish is recommended.

(2) Regular physical activity: Recommended exercise for patients aged 60 years and older: peak heart rate 110/minute, for 30-40 minutes a day, 3-5 days a week.

(3) Weight reduction.

(4) Moderation of alcohol intake, smoking cessation. 5. Pharmacologic Treatment:

1) Initial drug therapy. First choice: Long-acting (once or twice a day) Ca antagonists or ACE inhibitors. Second choice: Thiazide diuretics (combined with potassium-sparing diuretic).

2) Combination therapy.

(1) For patients without complications, either of the following is recommended.
i) Ca antagoinst + ACE inhibitor,
ii) ACE inhibitor + Ca antagonist (or low-dose diuretics),
iii) diuretic + Ca antagonist (or ACE inhibitor), iv) beta-blockers, alpha 1-blockers, alpha + beta blockers can be used according to the patho-physiological state of the patient.

(2) For patients with complications. Drug(s) should be selected according to each complication.

3) Relatively contraindicated drugs. beta-Blockers and alpha 1-blockers are relatively contraindicated in elderly patients with hypertension in Japan. Centrally acting agents such as reserpine, methyldopa and clonidine are also relatively contraindicated beta-Blockers are contraindicated in patients with congestive heart failure, arteriosclerosis obliterans, chronic obstructive pulmonary disease, diabetes mellitus (or glucose intolerance), or bradycardia. These conditions are often present in elderly subjects. Elderly subjects are susceptible to alpha 1-blocker-induced orthostatic hypotension, since their baroreceptor reflex is diminished. Orthostatic hypotension may cause falls and bone fractures in the elderly.

Langsjoen P; Langsjoen P; Willis R; Folkers K
Institute for Biomedical Research, University of Texas at Austin 78712, USA.
Mol Aspects Med (England) 1994, 15 Suppl pS265-72

A total of 109 patients with symptomatic essential hypertension presenting to a private cardiology practice were observed after the addition of CoQ10 (average dose, 225 mg/day by mouth) to their existing antihypertensive drug regimen. In 80 per cent of patients, the diagnosis of essential hypertension was established for a year or more prior to starting CoQ10 (average 9.2 years). Only one patient was dropped from analysis due to noncompliance. The dosage of CoQ10 was not fixed and was adjusted according to clinical response and blood CoQ10 levels. Our aim was to attain blood levels greater than 2.0 micrograms/ml (average 3.02 micrograms/ml on CoQ10). Patients were followed closely with frequent clinic visits to record blood pressure and clinical status and make necessary adjustments in drug therapy. Echocardiograms were obtained at baseline in 88% of patients and both at baseline and during treatment in 39% of patients. A definite and gradual improvement in functional status was observed with the concomitant need to gradually decrease antihypertensive drug therapy within the first one to six months. Thereafter, clinical status and cardiovascular drug requirements stabilized with a significantly improved systolic and diastolic blood pressure. Overall New York Heart Association (NYHA) functional class improved from a mean of 2.40 to 1.36 (P < 0.001) and 51% of patients came completely off of between one and three antihypertensive drugs at an average of 4.4 months after starting CoQ10. Only 3% of patients required the addition of one antihypertensive drug. In the 9.4% of patients with echocardiograms both before and during treatment, we observed a highly significant improvement in left ventricular wall thickness and diastolic function.

Digiesi V; Cantini F; Oradei A; Bisi G; Guarino GC; Brocchi A; Bellandi F ; Mancini M; Littarru GP
Third institute of Clinical Medicine and Medical Therapy, University of Florence Medical School, Italy.
Mol Aspects Med (England) 1994, 15 Suppl ps257-63

This study was undertaken to clarify the mechanism of the antihypertensive effect of coenzyme Q10 (CoQ10). Twenty-six patients with essential arterial hypertension were treated with oral CoQ10, 50 mg twice daily for 10 weeks. Plasma CoQ10, serum total and high-density lipoprotein (HDL) cholesterol, and blood pressure were determined in all patients before and at the end of the 10-week period. At the end of the treatment, systolic blood pressure (SBP) decreased from 164.5 +/- 3.1 to 146.7 +/- 4.1 mmHg and diastolic blood pressure (DBP) decreased from 98.1 +/- 1.7 to 86.1 +/- 1.3 mmHg (P < 0.001). Plasma CoQ10 values increased from 0.64 +/- 0.1 microgram/ml to 1.61 +/- 0.3 micrograms/ml (P < 0.02). Serum total cholesterol decreased from 222.9 +/- 13 mg/dl to 213.3 +/- 12 mg/dl (P < 0.005) and serum HDL cholesterol increased from 41.1 +/- 1.5 mg/dl to 43.1 +/- 1.5 mg/dl (P < 0.01). In a first group of 10 patients serum sodium and potassium, plasma clinostatic and orthostatic renin activity, urinary aldosterone, 24-hour sodium and potassium were determined before and at the end of the 10-week period. In five of these patients peripheral resistances were evaluated with radionuclide angiocardiography. Total peripheral resistances were 2,283 +/- 88 dyne.s.cm-5 before treatment and 1,627 +/- 158 dyn.s.cm-5 after treatment (P < 0.02). Plasma renin activity, serum and urinary sodium and potassium, and urinary aldosterone did not change. In a second group of 11 patients, plasma endothelin, electrocardiogram, two-dimensional echocardiogram and 24-hour automatic blood pressure monitoring were determined.

Langsjoen H; Langsjoen P; Langsjoen P; Willis R; Folkers K
University of Texas Medical Branch, Galveston 77551, USA.
Mol Aspects Med (England) 1994, 15 Suppl ps165-75

Over an eight year period (1985-1993), we treated 424 patients with various forms of cardiovascular disease by adding coenzyme Q10 (CoQ10) to their medical regimens. Doses of CoQ10 ranged from 75 to 600 mg/day by mouth (average 242 mg). Treatment was primarily guided by the patient's clinical response. In many instances, CoQ10 levels were employed with the aim of producing a whole blood level greater than or equal to 2.10 micrograms/ml (average 2.92 micrograms/ml, n = 297). Patients were followed for an average of 17.8 months, with a total accumulation of 632 patient years. Eleven patients were omitted from this study: 10 due to non-compliance and one who experienced nausea. Eighteen deaths occurred during the study period with 10 attributable to cardiac causes. Patients were divided into six diagnostic categories: ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM), primary diastolic dysfunction (PDD), hypertension (HTN), mitral valve prolapse (MVP) and valvular heart disease (VHD). For the entire group and for each diagnostic category, we evaluated clinical response according to the New York Heart Association (NYHA) functional scale, and found significant improvement. Of 424 patients, 58 per cent improved by one NYHA class, 28% by two classes and 1.2% by three classes. A statistically significant improvement in myocardial function was documented using the following echocardiographic parameters: left ventricular wall thickness, mitral valve inflow slope and fractional shortening. Before treatment with CoQ10, most patients were taking from one to five cardiac medications. During this study, overall medication requirements dropped considerably: 43% stopped between one and three drugs. Only 6% of the patients required the addition of one drug. No apparent side effects from CoQ10 treatment were noted other than a single case of transient nausea. In conclusion, CoQ10 is a safe and effective adjunctive treatment for a broad range of cardiovascular diseases, producing gratifying clinical responses while easing the medical and financial burden of multidrug therapy.

Danysz A; Oledzka K; Bukowska-Kiliszek M
Department of Pharmacology, Pharmaceutical Research Institute Rydygiera, Warszawa, Poland.
Pol J Pharmacol (Poland) Sep-Oct 1994, 46 (5) p457-61

Administration of coenzyme Q-10 (10 mg/kg) once a day for 4 weeks decreased the arterial blood pressure in SHR's. Enalapril and nitrendipine administered in a single dose caused significant decrease of blood pressure. Application of enalapril and nitrendipine to rats chronically pretreated with coenzyme Q-10 revealed, that the maximal hypotensive effect was not greater, but it lasted much (ca. 2-times) longer. Independently of mechanism of this interaction it may be suggested that the chronic administration of coenzyme Q-10 would create the possibility of significant decrease of the frequency of some antihypertensive drug administration.

Langsjoen PH; Langsjoen PH; Folkers K
Clin Investig (Germany) 1993, 71 (8 Suppl) pS140-4

Symptoms of fatigue and activity impairment, atypical precordial pain, and cardiac arrhythmia frequently precede by years the development of congestive heart failure. Of 115 patients with these symptoms, 60 were diagnosed as having hypertensive cardiovascular disease, 27 mitral valve prolapse syndrome, and 28 chronic fatigue syndrome. These symptoms are common with diastolic dysfunction, and diastolic function is energy dependent. All patients had blood pressure, clinical status, coenzyme Q10 (CoQ10) blood levels and echocardiographic measurement of diastolic function, systolic function, and myocardial thickness recorded before and after CoQ10 replacement. At control, 63 patients were functional class III and 54 class II; all showed diastolic dysfunction; the mean CoQ10 blood level was 0.855 micrograms/ml; 65%, 15%, and 7% showed significant myocardial hypertrophy, and 87%, 30%, and 11% had elevated blood pressure readings in hypertensive disease, mitral valve prolapse and chronic fatigue syndrome respectively. Except for higher blood pressure levels and more myocardial thickening in the hypertensive patients, there was little difference between the three groups. CoQ10 administration resulted in improvement in all; reduction in high blood pressure in 80%, and improvement in diastolic function in all patients with follow-up echocardiograms to date; a reduction in myocardial thickness in 53% of hypertensives and 36% of the combined prolapse and fatigue syndrome groups; and a reduced fractional shortening in those high at control and an increase in those initially low.

Okamoto H; Kawaguchi H; Togashi H; Minami M; Saito H; Yasuda H
Department of Cardiovascular, Hokkaido University, Japan.
Biochem Med Metab Biol (United States) Apr 1991, 45 (2) p216-26

To test the hypothesis that structural abnormalities exist in the kidney membrane of spontaneously hypertensive rats, we examined the effect of long-term administration of coenzyme Q10 on membrane lipid alterations in the kidney of stroke-prone spontaneously hypertensive rats (SHRSP). As compared with normotensive Wistar-Kyoto rats, renal membrane phospholipids, especially phosphatidylcholine and phosphatidylethanolamine, decreased and renal phospholipase A2 activity was enhanced with age in untreated SHRSP. Treatment with coenzyme Q10 attenuated the elevation of blood pressure, the membranous phospholipid degradation, and the enhanced phospholipase A2 activity. These results suggest that one factor contributing to the progress of hypertension is a structural membrane abnormality that alters the physical and functional properties of the cell membrane, and coenzyme Q10 might protect the renal membrane from damage due to hypertension in SHRSP.

Greenberg S; Frishman WH
Department of Medicine, Mt. Sinai Hospital and Medical Center, New York, New York
J Clin Pharmacol (United States) Jul 1990, 30 (7) p596-608

Co-enzyme Q10 (ubiquinone) is a naturally occurring substance which has properties potentially beneficial for preventing cellular damage during myocardial ischemia and reperfusion. It plays a role in oxidative phosphorylation and has membrane stabilizing activity. The substance has been used in oral form to treat various cardiovascular disorders including angina pectoris, hypertension, and congestive heart failure. Its clinical importance is now being established in clinical trails worldwide.

Greenberg SM; Frishman WH
Department of Medicine, Mt. Sinai Hospital and Medical School, New York, New York
Med Clin North Am (United States) Jan 1988, 72 (1) p243-58

A biochemical rationale for using CoQ in treating certain cardiovascular diseases has been established. CoQ subserves an endogenous function as an essential cofactor in several metabolic pathways, particularly oxidative respiration. As an exogenous source in supraphysiologic doses, CoQ may have pharmacologic effects that are beneficial to tissues rendered ischemic and then reperfused. Its mechanism of action appears to be that of a free radical scavenger and/or direct membrane stabilizer. Initial clinical studies performed abroad and in the United States indicate that CoQ may be effective in treating certain patients with ischemic heart disease, congestive heart failure, toxin-induced cardiotoxicity, and possibly hypertension. The most intriguing property of CoQ is its potential to protect and preserve ischemic myocardium during surgery. Currently, CoQ is still considered an experimental agent and only further studies will determine whether it will be useful therapy for human cardiovascular disease states.

Folkers K; Drzewoski J; Richardson PC; Ellis J; Shizukuishi S; Baker L
Res Commun Chem Pathol Pharmacol (United States) Jan 1981, 31 (1) p129-40

Six untreated hypertensive patients and ten on therapy, but having elevated blood pressures, were treated with coenzyme Q10(CoQ10); 14/16 patients showed reductions (p less than 0.05-less than 0.001) in systolic pressures; 11/16 showed reductions (p less than 0.05-less than 0.001) in diastolic pressure; 9/10 showed reductions of elevated pressures to a normal range. By impedance cardiography and electrocardiography, there were no changes in cardiac outputs, stroke volumes and Heather Indices except for a few patients with changes of doubtful biological significance. 3/16 patients had exceptionally low basal specific activities of the succinate dehydrogenase-coenzyme Q10 reductase in blood which increased to a normal range on treatment. A greater deficiency of CoQ10 in the vascular system than in blood is likely. We consider that (1) the mechanism of reduction of elevated blood pressures by CoQ10 is based upon normalization or autoregulation of peripheral resistance rather than cardiac regulation, and (2) that the therapeutic activity of CoQ10 is not pharmacodynamic, but results from a translational increase in levels of CoQ10-enzymes in vascular tissue during ca. 4-12 weeks.

Yamagami T; Shibata N; Folkers K
Res Commun Chem Pathol Pharmacol (United States) Aug 1976, 14 (4) p721-7

Coenzyme Q10 has been administered to five patients having essential hypertension and deficiencies of activity of succinate dehydrogenase-co-enzyme Q10 reductase in leucocyte preparations ranging from 20-40%. For a 74-year old male, the systolic pressure was reduced (p less than 0.001), the diastolic pressure was reduced (p less than 0.05), the specific activity of the coenzyme Q10-enzyme was increased (p less than 0.001), and the deficiency of coenzyme Q10 activity was negated (p less than 0.01). Four patients receiving CoQ10 for 3-5 months showed reductions (p less than 0.05 to p less than 0.001) of diastolic pressure, and 3 of these 4 showed reductions (p less than 0.05 to p less than 0.01) of diastolic pressure. Initial deficiencies of enzyme activity were reduced (p less than 0.01 to 0.05) in two patients. Three other patients did not show the high level of deficiency on treatment as initially observed. These effects of CoQ10 on the reduction of systolic and diastolic blood pressures, increase in CoQ10-enzyme activity, and reduction of CoQ10-deficiency are presumably due to improved bioenergetics through correction of a deficiency of coenzyme Q10.

Kishi H; Kishi T; Folkers K
Res Commun Chem Pathol Pharmacol (United States) Nov 1975, 12 (3) p533-40

Background data revealed that some American and Japanese patients with essential hypertension, including many who were not being treated with any anti-hypertensive drug, had a deficiency of coenzyme Q10. Eight clinically used anti-hypertensive drugs have now been tested for inhibition of two mitochondrial coenzyme Q10-enzymes of heart tissue, succinoxidase and NADH-oxidase. Diazoxide and propranolol significantly inhibited the CoQ10-succinoxidase and CoQ10-NADH-oxidase, respectively. Metoprolol did not inhibit succinoxidase, and was one-fourth as active as propranolol for inhibition of NADH-oxidase. Hydrochlorothiazide, hydralazine, ans clonidine also inhibited CoQ10-NADH-oxidase. Reserpine did not inhibit either CoQ10-enzyme, and methyldopa was a very eak inhibitor of succinoxidase. The internationally recognized clinical side-effects of propranolol may be due, in part, to inhibition of CoQ10-enzymes which are indispensable in the bioenergetics of cardiac function. A pre-existing deficiency of coenzyme Q10 in the myocardium of hypertensive patients could be augmented by subsequent treatment with propranolol, possibly to the "life-threatening" state described by others.

Yamagami T; Shibata N; Folkers K
Res Commun Chem Pathol Pharmacol (United States) Jun 1975, 11 (2) p273-88

The specific activities (S.A.) of the succinate dehydrogenase-coenzyme Q10 (CoQ10) reductase of a control group of 65 Japanese adults and 59 patients having essential hypertension were determined. The mean S.A. of the hypertensive group was significantly lower (p less than 0.001) and the mean % deficiency of enzyme activity was significantly higher (p less than 0.001) than the values for the control group. These data on Japanese in Osaka agree with data on Americans in Dallas. Some patients showed no CoQ10-deficiency, and others showed definite deficiencies. Emphasizing the CoQ10-enzyme for patient selection, CoQ10 was administered to hypertensive patients. Four individuals showed significant but partial reductions of blood pressure. Monitoring the CoQ10-enzyme before, during, and after administration of CoQ10 indicated responses. The maintenance of high blood pressure could be primarily due to contraction of the arterial wall. Contraction or relaxation of an arterial wall is dependent upon bioenergetics, which also provide the energy for biosynthesis of angiotensin II, renin, aldosterone, and the energy for sodium and potassium transport. A clinical benefit from administration of CoQ10 to patients with essential hypertension could be based upon correcting a deficiency in bioenergetics, and point to possible combination treatments with a form of CoQ and anti-hypertensive drugs.

Resch KL; Ernst E
Postgraduate Medical School, University of Exeter, UK.
Fortschr Med (Germany) Jul 20 1995, 113 (20-21) p311-5

A good deal of evidence suggests beneficial effects of the regular dietary intake of garlic on mild hypertension and hyperlipidemia. Garlic seems to have anti-microbial and immunostimulating properties, enhance fibrinolytic activity, and exert favorable effects on platelet aggregation and adhesion. Standardised preparations guarantee exact dosing and minimize the problem of the strong odour of raw garlic. Thus, a traditional folk remedy has established its usefulness for many patients with less severe forms of cardiovascular disease as a medical drug with very few side effects. The available evidence gives rise to the hope that the list of indications may even be considerably extended in the future. (43 Refs.)

Silagy CA; Neil HA
Department of General Practice, Flinders University of South Australia, Adelaide.
J Hypertens (England) Apr 1994, 12 (4) p463-8

OBJECTIVE: To undertake a systematic review, including meta-analysis, of published and unpublished randomized controlled trials of garlic preparations to determine the effect of garlic on blood pressure relative to placebo and other antihypertensive agents.

DATA IDENTIFICATION: Studies were identified by a search of Medline and the Alternative Medicine electronic databases, from references listed in primary and review articles, and through direct contact with garlic manufacturers.

STUDY SELECTION: Only randomized controlled trials of garlic preparations that were at least 4 weeks in duration were deemed eligible for inclusion in the review.

DATA EXTRACTION: Data were extracted from the published reports by the two authors independently, with disagreements resolved by discussion.

RESULTS: Eight trials were identified (all using the same dried garlic powder preparation (Kwai) with data from 415 subjects included in the analyses. Only three of the trials were specifically conducted in hypertensive subjects, and many had other methodological shortcomings. Of the seven trials that compared the effect of garlic with that of placebo, three showed a significant reduction in systolic blood pressure (SBP) and four in diastolic blood pressure (DBP). The overall pooled mean difference in the absolute change (from baseline to final measurement) of SBP was greater in the subjects who were treated with garlic then in those treated with placebo. For DBP the corresponding reduction in the garlic-treated subjects was slightly smaller.

CONCLUSIONS: The results suggest that this garlic powder preparation may be of some clinical use in subjects with mild hypertension. However, there is still insufficient evidence to recommend it is a routine clinical therapy for the treatment of hypertensive subjects. More-rigorously designed and analysed trials are needed.

Estrada CA; Young MJ
Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan 48202.
J Gen Intern Med (United States) Nov 1993, 8 (11) p619-21

The authors used the N-of-1 clinical trial methodology to obtain insights about a patient's preference for garlic for the management of his hypertension. The 61-year-old man received garlic, 500 mg by mouth three times a day (3 weeks), or identical placebo (3 weeks) in three treatment pairs. While the patient was taking garlic the mean systolic blood pressure decreased by 2 mm Hg (95% confidence interval 0.4 to 4.7, p < 0.05), and the diastolic blood pressure decreased by 2.4 mm Hg (95% confidence interval 0.4 to 4, p < 0.025). The treatment effect of garlic was small, but the patient believed continuing garlic for the management of his hypertension was justified.

McMahon FG; Vargas R
Clinical Research Center, New Orleans, LA 70112.
Pharmacotherapy (United States) Jul-Aug 1993, 13 (4) p406-7

A popular garlic preparation containing 1.3% allicin at a large dose (2400 mg) was evaluated in this open-label study in nine patients with rather severe hypertension (diastolic blood pressure > or = 115 mm Hg). Sitting blood pressure fell 7/16 (+/- 3/2 SD) mm Hg at peak effect approximately 5 hours after the dose, with a significant decrease in diastolic blood pressure (p < 0.05) from 5-14 hours after the dose. No significant side effects were reported. Our results indicate that this garlic preparation can reduce blood pressure. Further controlled studies are needed, particularly with more conventional doses (e.g., < or = 900 mg/day), in patients with mild to moderate hypertension and under placebo-controlled, double-blind conditions.

Auer W; Eiber A; Hertkorn E; Hoehfeld E; Koehrle U; Lorenz A; Mader F; Merx W; Otto G; Schmid-Otto B; et al
Incorporated Society, Nittendorf, West Germany.
Br J Clin Pract Symp Suppl (England) Aug 1990, 69 p3-6

Forty-seven non-hospitalised patients with mild hypertension took part in a randomised, placebo-controlled, double-blind trial conducted by 11 general practitioners. The patients who were admitted had diastolic blood pressures between 95 and 104 mmHg after a two-week acclimatization phase. The patients then took either a preparation of garlic powder (Kwai) or a placebo of identical appearance for 12 weeks. Blood pressure and plasma lipids were monitored during treatment after four, eight and 12 weeks. Significant differences between the placebo and the drug group were found during the course of therapy. For example, the supine diastolic blood pressure in the group having garlic treatment fell from 102 to 91 mmHg after eight weeks (p less than 0.05) and to 89 mmHg after 12 weeks (p less than 0.01). The serum cholesterol and triglycerides were also significantly reduced after eight and 12 weeks of treatment. In the placebo group, on the other hand, no significant changes occurred.

Umemura S; Smyth DD; Pettinger WA
J Hypertens (England) Apr 1985, 3 (2) p159-65

We activated three known components of the adenylate cyclase system in renal membranes from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. The basal adenylate cyclase activity and responses to plasma membrane receptor activation by parathyroid hormone, isoproterenol and vasopressin were not different between the two strains. The response to prostaglandin E2 (PGE2), however, was less in the SHR than in the WKY at five, (P less than 0.05), 12 (P less than 0.01) and 16 (P less than 0.01) weeks of age. Activation of either the guanosine-5'-triphosphate (GTP) binding regulatory protein (N) with sodium fluoride (NaF) and guanyl-5'-yl-imidodiphosphate [Gpp(NH)p], or the catalytic unit with manganese chloride (MnCl2) or forskolin were not different between the two groups. When the medullary and cortical plasma membrane adenylate cyclase responses were studied separately, the observed decreased response to PGE2 (of SHR) was found to be entirely in the cortex. Also, the NaF response was reduced in the cortical region of the 12-week-old rats, a finding suggesting a possibility of a post receptor defect. These results show that there is a defective renal adenylate cyclase response specific to prostaglandin E2 in SHR. This defect could be related to the development of hypertension, by changing the natriuretic and/or renal vasodilating effects

Higashi Y; Oshima T; Watanabe M; Matsuura H; Kajiyama G
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Hypertension (United States) Mar 1996, 27 (3 Pt 2) p643-8

This study examined whether disturbances in nitric oxide formation contribute to renal dysfunction in salt-sensitive essential hypertensive patients. We evaluated the effects of intravenous administration of L-arginine (500 mg/kg given over 30 minutes) on systemic and renal hemodynamics in 23 patients with mild essential hypertension during 1 week of a low NaCl diet (50 mmol/d) followed by 1 week of a high NaCl diet (340 mmol/d). Patients were classified as salt sensitive (n=10) or salt resistant (n=13) based on salt-induced changes in their blood pressures. Salt loading increased renal vascular resistance but not renal plasma flow in salt-sensitive patients. The L-arginine-induced renovascular relaxation was significantly reduced by a high NaCl diet (renal vascular resistance: low NaCl -12.4 +/- 2.3% versus high NaCl -7.1 +/- 1.8%, P < .001) in salt-sensitive patients, whereas it was unchanged in salt-resistant patients. The increase in plasma cGMP in response to L-arginine was also reduced by a high NaCl diet in the salt-sensitive patients (low NaCl 49 +/- 7% versus high NaCl 36 +/- 8%, P < .05) but not in the salt-resistant patients (low NaCl 51 +/- 6% versus high NaCl 58 +/- 6%). These findings suggest that NaCl loading in salt-sensitive patients with mild essential hypertension reduces the ability of L-arginine to produce nitric oxide in the endothelium of the renal vasculature.

Kitazono T; Faraci FM; Heistad DD
Department of Internal Medicine, Cardiovascular Center, University of Iowa College of Medicine, Iowa City 52242, USA.
Hypertension (United States) Apr 1996, 27 (4) p893-6

The objective of this study was to test the hypothesis that administration of L-arginine, a substrate for nitric oxide synthase, restores acetylcholine-induced dilatation of the basilar artery in chronically hypertensive rats. Basilar artery diameter was measured through a cranial window in anesthesized stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) aged 6 to 7 months (adult) and 12 months (older adult). Under control conditions, baseline basilar artery diameter was smaller in SHRSP (adult, 239 +/- 30 micron; older adult, 198 +/- 13 micron) (mean +/- SE) than in WKY (adult, 261 +/- 10 micron; older adult, 259 +/- 7 micron) (P <.05 versus SHRSP). Topical application of acetylcholine (10(-5) mol/L) produced dilatation of the basilar artery in WKY, which was impaired in both adult and older SHRSP (P <.05). Topical L-arginine (10(-3) mol/L for 30 minutes) did not affect responses to acetylcholine in adult SHRSP but enhanced vasodilatation in response to acetylcholine (10(-5) mol/L) in older SHRSP without affecting responses to sodium nitroprusside. In contrast, D-arginine did not affect acetylcholine-induced vasodilatation in older SHRSP. These results suggest that impaired dilatation of the basilar artery in response to acetylcholine in older SHRSP is restored toward normal by L-arginine, a substrate for nitric oxide synthase.

Salonen JT; Salonen R; Ihanainen M; Parviainen M; Seppanen R; Seppanen K; Rauramaa R
Department of Community Health, University of Kuopio, Finland.
J Hypertens Suppl (England) Dec 1987, 5 (5) pS521-4

We investigated the association of dietary fatty acids and plasma antioxidative vitamins with blood pressure in 722 eastern Finnish men aged 54 years, examined in the Kuopio Ischaemic Heart Disease Risk Factor Study in 1984-1986, who had no known hypertension nor any cerebrovascular disease. Allowing for the major anthropometric, dietary, medical and psychological determinants of blood pressure in a multivariate regression analysis, plasma ascorbic acid concentration had a moderate, independent inverse association (P less than 0.0001) and the estimated dietary intake of linolenic acid an inverse (P = 0.026) independent association with mean resting blood pressure. The marked elevation of blood pressure at the lowest levels of plasma Vitamin-C concentration supports the hypothesis of the role of antioxidants in the aetiology of hypertension.

Toda N
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
J Diabetes Complications (United States) Oct-Dec 1995, 9 (4) p200-2

We discovered vasodilator innervation first in canine cerebral arteries, in which nitric oxide (NO) acts as a neurotransmitter; thus, the nerve is called nitroxidergic. Then, reciprocal innervation of noradrenergic and nitroxidergic nerves in canine peripheral arteries was determined; adrenergic nerve-mediated vasoconstriction is predominant over vasodilatation mediated by NO derived from the nerve. In anesthetized dogs, hypertension induced by NO synthase inhibitors is suppressed by hexamethonium. It is hypothesized that impairment of nitroxidergic nerve function by NO synthase inhibition is mainly involved in the genesis of hypertension.

Taddei S; Virdis A; Ghiadoni L; Salvetti A
Cattedra di Medicina Interna, Universita degli Studi di Pisa.
Ann Ital Med Int (Italy) Oct 1995, 10 Suppl p85S-90S

In normotensive humans, the endothelium modulates vascular tone mainly by the production of nitric oxide. In human essential hypertension the basal release of nitric oxide is reduced and forearm vasodilation to the endothelium-dependent agonists acetylcholine or bradykinin is blunted. Defective basal release of nitric oxide seems to be secondary to blood pressure increase while impaired agonist-evoked endothelium-dependent vasodilation is probably a primary phenomenon. This latter endothelial dysfunction seems to be caused by the simultaneous presence of an alteration in the L-arginine-nitric oxide pathway and the production of constrictor prostanoids. Defective nitric oxide production is already detectable in normotensive offspring of hypertensive patients and young essential hypertensives. In contrast, vasoconstrictor prostanoid production seems to be associated with aging. In essential hypertensive patients, although only scanty data are available, chronic effective pharmacological treatment seems to restore impaired basal production of nitric oxide but does not improve vascular response to endothelial agonists. (34 Refs.)

Mimran A; Ribstein J; DuCailar G
Department of Medicine, Centre Hospitalier Universitaire, Montpellier, France.
Hypertension (United States) Dec 1995, 26 (6 Pt 1) p937-41

We assessed the renal hemodynamic response to L-arginine infusion (30 g within 60 minutes) in normotensive subjects, patients with never-treated essential hypertension, and hypertensive patients controlled by long-term (more than 2 years) treatment with or without an angiotensin-converting enzyme inhibitor. The renal vasodilator response to L-arginine observed in normotensive subjects (15 +/- 4% increase in effective renal plasma flow) was abolished in untreated hypertensive patients and restored only in the group treated by angiotensin-converting enzyme inhibition. In the whole population a positive correlation between the change in effective renal plasma flow and the change in urinary cGMP was obtained. It is suggested that abnormalities of the renal nitric oxide pathway not corrected by increased availability of L-arginine and reversible only on long-term treatment by angiotensin-converting enzyme inhibition may underlie the abnormal renal resistance observed in essential hypertension.

Ascherio A; Hennekens C; Willett WC; Sacks F; Rosner B; Manson J; Witteman J; Stampfer MJ
Department of Nutrition, Harvard School of Public Health, Boston, Mass 02115, USA.
Hypertension (United States) May 1996, 27 (5) p1065-72

We examined prospectively the relation of nutritional factors with hypertension and blood pressure levels among 41,541 predominantly white US female nurses, aged 38 to 63 years, who completed a detailed semiquantitative food frequency questionnaire in 1984 and were without diagnosed hypertension, cancer, or cardiovascular disease. During 4 years of follow-up, from 1984 to 1988, 2,526 women reported a diagnosis of hypertension. Age, relative weight, and alcohol consumption were the strongest predictors for the development of hypertension. Dietary calcium, magnesium, potassium, and fiber were not significantly associated with risk of hypertension, after adjusting for age, body mass index, alcohol, and energy intake. Among women who did not report hypertension during the follow-up period, calcium, magnesium, potassium, and fiber were each significantly inversely associated with self-reported systolic and diastolic pressures, after adjusting for age, body mass index, alcohol consumption, and energy intake. When the four nutrients were added simultaneously to the regression model, only fiber and magnesium intakes retained significant inverse associations with systolic and diastolic pressures. In analyses of food groups, intakes of fruit and vegetables were inversely associated with systolic and diastolic pressures, and intakes of cereals and meat were directly associated with systolic pressure. These results support hypotheses that age, body weight, and alcohol consumption are strong determinants of risk of hypertension in middle-aged women. They are compatible with the possibilities that magnesium and fiber as well as a diet richer in fruits and vegetables may reduce blood pressure levels.

Saito N
Nippon Rinsho (Japan) Jan 1996, 54 (1) p59-66

It is known that the peroxidation of LDL is a trigger for developing arteriosclerosis. The oxidized LDL is produced by either oxidative stress or a few oxidant. Selenium decreased in serum and some organs of stroke-prone spontaneously hypertensive rats (SHRSP), which is a cofactor of glutamine peroxidase. Serum magnesium decreased in patients with diabetes mellitus, with ischemic heart disease, with essential hypertension and with cerebral vascular lesions. Calcium to magnesium ratio was higher in some organs of SHRSP as compared to Wistar Kyoto rats (WKY). These changes accelerated vascular lesions in SHRSP.

Davydenko NV; Smirnova IP; Kvasha EA; Gorbas' IM; Koblianskaia AV
Vopr Pitan (Russia) 1995, (6) p17-9

1556 of men living in Kiev aged 20-59 years were examined to evaluate interrelationship between the dietary intakes of Ca, Mg, P, Fe, Cu, Zn and level of arterial blood pressure (AP). Dietary intake was studied by 24-h recall methodology. Systolic AP > 160 mm Hg and/or diastolic AP > 90 mm Hg were referred as arterial hypertension (AH). It was shown that high dietary intakes of Ca or Zn were related with the higher rate of AH. At low level of dietary intake of Mg, Cu or P the prevalence of AH was seen in 1.8-2 times more often than at high level of intake of these micronutrients. Mean systolic AP had trend to increasing and diastolic AP was significant higher at low level of dietary intake of P. Correction of dietary intake of microelements should be used in preventive measures of AH.

Wu X; Ackermann U; Sonnenberg H
Department of Physiology, University of Toronto, Ontario, Canada.
Clin Exp Hypertens 1995 Aug;17(6):989-1008

Weanling male inbred Dahl rats (Jr salt-sensitive (S) and salt-resistant (R) strains) were placed on high (4%, HK) and low (0.2%, LK) potassium diets for 4 weeks. Both diets contained 8% sodium chloride, 2.5% calcium, 0.8% magnesium, and 2.0% phosphorous. Balance studies were carried out during the final week on the diets. Mean arterial blood pressure was determined, and dietary intake and urinary output of water, sodium, chloride, potassium, calcium, magnesium, and phosphate were monitored daily during this period. The data show that blood pressures of S rats were significantly higher than those of R rats on both HK and LK diets; however, reduced dietary potassium was associated with increased blood pressure in both strains. Urinary excretions of calcium and magnesium were higher, and urinary phosphate excretion was lower, in S compared to R rats. Decreased potassium intake was associated with increased excretion of calcium, magnesium and phosphate in both strains. The changes in calcium and magnesium excretion were significantly correlated to blood pressure across strains and diets. We conclude that the effects of a high salt diet on increasing blood pressure can be potentiated by lack of potassium, even in previously salt-resistant rats. Increased blood pressure is associated with increased divalent cation excretion. It is not yet known whether this is a cause-and-effect relationship.

Seelig MS
Department of Nutrition, School of Public Health, University of North Carolina, Chapel Hill.
J Am Coll Nutr (United States) Oct 1994, 13 (5) p429-46

Stress intensifies release of catecholamines and corticosteroids that increase survival of normal animals when their lives are threatened. When magnesium (Mg) deficiency exists, stress paradoxically increases risk of cardiovascular damage including hypertension, cerebrovascular and coronary constriction and occlusion, arrhythmias and sudden cardiac death (SCD). In affluent societies, severe dietary Mg deficiency is uncommon, but dietary imbalances such as high intakes of fat and/or calcium (Ca) can intensify Mg inadequacy, especially under conditions of stress. Adrenergic stimulation of lipolysis can intensify its deficiency by complexing Mg with liberated fatty acids (FA), A low Mg/Ca ratio increases release of catecholamines, which lowers tissue (i.e. myocardial) Mg levels. It also favors excess release or formation of factors (derived both from FA metabolism and the endothelium), that are vasoconstrictive and platelet aggregating; a high Ca/Mg ratio also directly favors blood coagulation, which is also favored by excess fat and its mobilization during adrenergic lipolysis. Auto-oxidation of catecholamines yields free radicals, which explains the enhancement of the protective effect of Mg by anti-oxidant nutrients against cardiac damage caused by beta-catecholamines. Thus, stress, whether physical (i.e. exertion, heat, cold, trauma--accidental or surgical, burns), or emotional (i.e. pain, anxiety, excitement or depression) and dyspnea as in asthma increases need for Mg. Genetic differences in Mg utilization may account for differences in vulnerability to Mg deficiency and differences in body responses to stress.

Joffres MR; Reed DM; Yano K
Am J Clin Nutr (United States) Feb 1987, 45 (2) p469-75

Associations between blood pressure and intakes of 61 dietary variables assessed by 24-h recall method were investigated in 615 men of Japanese ancestry living in Hawaii who had no history of cardiovascular disease or treated hypertension. Magnesium, calcium, phosphorus, potassium, fiber, vegetable protein, starch, Vitamin-C, and vitamin D intakes were significant variables that showed inverse associations with blood pressure in univariate and a multivariate analyses. Magnesium had the strongest association with blood pressure, which supports recent interest in its relation to blood pressure. Nevertheless, it was not possible to separate the effect of magnesium from that of other variables because of the problem of high intercorrelation among many nutrients. While recommendations based upon cross-sectional studies must be viewed cautiously, these results suggest that foods such as vegetables, fruits, whole grains, and low-fat dairy items are major sources of nutrients that may be protective against hypertension.

Fujita T; Ando K
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
Nippon Naibunpi Gakkai Zasshi (Japan) May 20 1994, 70 (4) p423-30

Sodium (Na) intake is one of the important environmental factors influencing the development and maintenance of high blood pressure (BP). Patients with essential hypertension can be divided into two groups: "salt-sensitive" and "non-salt-sensitive", according to BP response to salt loading, suggesting the heterogeneity of salt sensitivity of BP. Salt-sensitive patients had greater increases in BP by salt loading, associated with greater Na retention. Although the precise mechanism for impaired renal Na handling in salt-sensitive patients is still unknown, the sympathetic nervous system in the kidney may play an important role in the decreased renal function of Na excretion and the increased salt sensitivity. Moreover, there are several pieces of evidence indicating that increased renal sympathetic nerve activity is intimately related to the abnormal central noradrenergic systems. In addition, the renin-angiotensin system, insulin, and so on, may modulate salt sensitivity of BP. Some ions influence the hypertensinogenic effect of Na: Chloride ion facilitates it, while potassium, calcium and magnesium antagonize it. Moreover, obesity and a stressful environment increase salt sensitivity of BP.

Adachi M; Nara Y; Mano M; Yamori Y
Department of Pathology, Shimane Medical University, Izumo, Japan.
Clin Exp Hypertens (United States) May 1994, 16 (3) p317-26

The effects of dietary magnesium (Mg) supplementation on intralymphocytic free Ca2+ ([Ca2+]i) and Mg2+ ([Mg2+]i) were examined in the stroke-prone spontaneously hypertensive rats (SHRSP) at the age of 10 weeks. After 40 day Mg supplementation (0.8% Mg in the diet), systolic blood pressure (SBP) was significantly lower in Mg supplemented group (Mg group) than the control group (0.2% Mg). [Ca2+]i was significantly lower and [Mg2+]i was significantly higher in Mg group than in the control group. Further, [Ca2+]i was positively and [Mg2+]i was negatively correlated with SBP. These results suggest that dietary Mg supplementation modifies [Ca2+]i and [Mg2+]i, and modulates the development of hypertension.

Engler MB; Engler MM; Ursell PC
University of California, Department of Physiological Nursing, San Francisco, 94143-0610, USA.
J Cardiovasc Risk (England) Jun 1994, 1 (1) p75-80

BACKGROUND: Dietary consumption of fish, rich in n-3 polyunsaturated fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has been shown to reduce blood pressure in both animal studies and clinical trials. Although the antihypertensive mechanisms are not known, the blood-pressure-lowering effect of n-3 polyunsaturated fatty acids may be partially attributed to their vasorelaxant properties.

METHODS: Aortic rings with and without endothelium, from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR), 16-17 weeks old, were suspended in tissue baths and isometric tension was measured. Concentration-response curves were generated for DHA and EPA (1-100 mu mol/l) in norepinephrine-contracted rings. Blood pressure was measured using the tail-cuff method and aortic media thickness was determined.

RESULTS: Blood pressure was significantly increased in SHR (n=10; 194 +/- 4.4 mmHg) compared with WKY (n=10; 124 +/- 1.2 mmHg, P < or = 0.0001). DHA (1-100 mu mol/l) relaxed aortic rings f rom WKY (-3.3 +/- 0.7 to -13 +/- 2.3%, P < or = 0.001) and from SHR (-6.5 +/- 1.8 to -22.9 +/- 4%, P < or = 0.01) in a concentration-dependent manner. EPA (1-100 mu mol/l) evoked greater relaxation in SHR (-10.1 +/- 2.0 to -33 +/- 3.9%, P < 0.01) than in WKY (-2.9 +/- 1.1 to -18.3 +/- 2.1%, P < 0.01) aortic rings. The relaxant effect of DHA in both WKY and SHR and of EPA in WKY were not dependent on an intact endothelium. However, EPA (1-10 mu mol/l) induced greater responses in intact SHR rings (-10.1 +/- 2.0 to -14.5 +/- 3.1%) than in de-endothelialized SHR rings (0 to -2.1 +/- 1.7%, P = 0.001).

CONCLUSION: The direct relaxant effects of n-3 fatty acids as seen in WKY and SHR may contribute, in part, toward the blood-pressure-lowering effect of dietary fish and fish-oil supplementation.

D'Almeida A; Carter JP; Anatol A; Prost C
Nutrition Program, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA.
Women Health (United States) 1992, 19 (2-3) p117-31

In a placebo controlled, partially double-blinded, clinical trial, a combination of evening primrose oil and fish oil was compared to Magnesium Oxide, and to a Placebo in preventing Pre-Eclampsia of Pregnancy. All were given as nutritional supplements for six months to a group of primiparous and multiparous pregnant women. Some of these women had personal or family histories of hypertension (21%). Only those patients who received prenatal care at the Central Maternity Hospital for Luanda were included in the study. Compared to the Placebo group (29%), the group receiving the mixture of evening primrose oil and fish oil containing Gamma-linolenic acid (GLA), Eicosapentaenoic acid (EPA), and Docosahexaenoic acid (DHA) had a significantly lower incidence of edema (13%, p = 0.004). The group receiving Magnesium Oxide had statistically significant fewer subjects who developed hypertension of pregnancy. There were 3 cases of eclampsia, all in the Placebo group.

Ali M; Thomson M; Alnaqeeb MA; al-Hassan JM; Khater SH; Gomes SA
Department of Biochemistry, Faculty of Science, Kuwait University.
Prostaglandins Leukot Essent Fatty Acids (Scotland) Oct 1990, 41 (2) p95-9

Rabbits were given collagen and arachidonic acid intravenously. Blood pressure, platelet counts, plasma thromboxane-B2 (TXB2) and plasma 6-keto-prostaglandin F1 alpha, (6-keto-PGF1 alpha) were determined. Both thrombogenic agents, upon infusion of a lethal dose, caused thrombocytopenia, indicative of in vivo platelet aggregation and hypotension. These changes were associated with an increase in plasma levels of TXB2 and 6-keto-PGF1 alpha measured by radioimmunoassay (RIA). Pretreatment of rabbits with an aqueous extract of garlic (500 mgkg) provided protection from thrombocytopenia and hypotension. Thromboxane-B2 synthesis was significantly reduced in animals pretreated with garlic and then injected with a lethal dose of either collagen or arachidonic acid. The amount of TXB2 synthesized in these animals was not sufficient to induce thrombocytopenia or hypotension. All animals pretreated with garlic were well protected against the effects of collagen or arachidonate infusion, and no apparent symptoms were observed in these animals. These observations indicate that garlic may be beneficial in the prevention of thrombosis.

Petkov V
J Ethnopharmacol (Switzerland) Feb 1986, 15 (2) p121-32

Some data about the use of medicinal plants in Bulgarian traditional medicine in the Middle Ages and in modern times are presented and the results of 40-year-long experimental-pharmacological investigations on many medicinal plants used in Bulgarian traditional medicine are reviewed. In-depth discussion is presented on the investigations of garlic (Allium sativum L.), a plant widely used by Bulgarian people for treating different diseases. Data from studies on a large number of plants used for treatment of hypertension, infectious diseases and as diuretic and spasmolytic remedies are summarized.

Foushee DB; Ruffin J; Banerjee U
Cytobios (England) 1982, 34 (135-36) p145-52

The major objective of this study was to re-evaluate the effects of garlic on blood pressure with respect to its ability to provoke a decrease in blood pressure and to determine the length of time that this decrease would require. Spontaneously hypertensive rats were given three doses of garlic extract (0.1 ml/kg, 0.25 ml/kg, and 0.5 ml/kg) by oral injection. The blood pressures of these ether-anaesthetized rats were measured immediately before the extract was given, and then 0.5, 2, 4, 6, and 24 h after the extract was given. A blood pressure measurement was also taken at 48 h after extract administration for the 0.5 ml/kg dose. The Gilson Duograph System was used to measure blood pressure by the tail-cuff method. There was a marked decrease in the systolic blood pressure of all of the rats after three doses and the decrease occurred within 30 min in each case. Even though the average decreases for the 0.1 ml/kg and the 0.25 ml/kg doses were calculated as 51,25 mm Hg and 56.25 mm Hg, respectively, these doses were not sufficient to sustain the blood pressure in a normal range for more than 1 or 2 h. The 0.5 ml/kg dose, showing an average decrease of 65.7 mm Hg, was sufficient to provoke a decrease to a normal level and to sustain this decrease for up to 24 h. The results indicate that garlic is effective as a natural agent for the treatment of hypertension.

Klag MJ; Whelton PK
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
Ann Epidemiol (United States) Sep 1993, 3 (5) p571-5

The evidence that treatment of hypertension prevents stroke is incontrovertible. Several observations, however, suggest that improvements in the prevalence of antihypertensive treatment cannot explain all of the recent decline in stroke mortality. Changes in nutritional patterns may explain some of the observed decline. Prospective studies have demonstrated conclusively an independent, increasing risk of hemorrhagic, but not thrombotic, stroke at higher levels of alcohol use. Stroke mortality is associated inversely with fat and protein intake. Dietary sodium has been linked to stroke in ecologic studies but not in prospective studies. Ecologic studies have suggested that foods high in Vitamin-C and potassium protect against stroke; an inverse association of potassium intake with fatal stroke has been demonstrated in cohort studies. Two studies in humans also suggest a protective effect of serum selenium against subsequent stroke. Determination of the influence of nutrients on stroke incidence offers tantalizing opportunities for future research and possibly, intervention.

Deucher GP
Clinica Guilherme Paulo Deucher, Sao Paulo, Brazil.
EXS (Switzerland) 1992, 62 p428-37

A total of 1,265 patients with age-related diseases such as diabetes, arthritis, vascular disease and hypertension as well as 1,100 persons in diminished health without apparent disease, were treated with the metal chelator EDTA and antioxidants such as vitamin C, E, beta-carotene, selenium, zinc and chromium. Good results were observed in the majority of patients. This is encouraging for the initiation of controlled clinical trials.

Ceriello A; Giugliano D; Quatraro A; Lefebvre PJ
Cattedra di Diabetologia e Dietoterapia I Facolta di Medicina, Universita di Napoli, Italia.
Clin Sci (Colch) (England) Dec 1991, 81 (6) p739-42

1. In this study an acute anti-hypertensive effect of three anti-oxidant agents (Vitamin-C, thiopronine and glutathione) in hypertensive subjects and in both hypertensive and non-hypertensive diabetic patients is reported.

2. The antioxidants had no effect on blood pressure in healthy normal subjects at a dose of 6 mmol, but thiopronine and glutathione produced a significant hypotensive effect at a dose of 12 mmol.

3. These data suggest that antioxidants might have a dilatatory effect and that an imbalance of the nitric oxide-free radical interaction might facilitate the development of hypertension in humans.

Davydenko NV, Kolchinskii VI
Vopr Pitan 1983 Nov-Dec;(6):17-9

Interrelation was studied between Vitamin-C consumption and the prevalence of coronary heart disease and some risk factors in a non-organized male population in Kiev. A reverse relationship was established between Vitamin-C consumption, the prevalence of coronary heart disease and some risk factors, such as arterial hypertension, hyperlipoproteinemia and overweight.

McCarron DA; Morris CD; Henry HJ; Stanton JL
Science (United States) Jun 29 1984, 224 (4656) p1392-8

A data base of the National Center for Health Statistics, Health and Nutrition Examination Survey I (HANES I), was used to perform a computer-assisted, comprehensive analysis of the relation of 17 nutrients to the blood pressure profile of adult Americans. Subjects were 10,372 individuals, 18 to 74 years of age, who denied a history of hypertension and intentional modification of their diet. Significant decreases in the consumption of calcium, potassium, vitamin A, and Vitamin-C were identified as the nutritional factors that distinguished hypertensive from normotensive subjects. Lower calcium intake was the most consistent factor in hypertensive individuals. Across the population, higher intakes of calcium, potassium, and sodium were associated with lower mean systolic blood pressure and lower absolute risk of hypertension. Increments of dietary calcium were also negatively correlated with body mass. Even though these correlations cannot be accepted as proof of causation, they have implications for future studies of the association of nutritional factors and dietary patterns with hypertension in America.