N. D. Markandu

Lack of effect of oral magnesium on high blood pressure: a double blind study.

Seventeen unselected patients with mild to moderate essential hypertension and whose average supine blood pressure after two months observation with no treatment was 154/100 mm Hg were entered into a double blind randomised crossover study of one months treatment with magnesium aspartate (15 mmol magnesium/day) and treatment with placebo for a further month. This preparation of magnesium was well tolerated and did not cause diarrhoea. Despite a significant increase in plasma magnesium concentration and a significant increase in urinary excretion of magnesium while taking magnesium aspartate there was no fall in blood pressure compared with either treatment with placebo or values before treatment. The results provide no evidence for a role of dietary magnesium in the regulation of high blood pressure and are contrary to recent speculations.

Essential hypertension: effect of an oral inhibitor of angiotensin-converting enzyme.

Captopril, a specific oral inhibitor of angiotensin-converting enzyme, was given to 18 unselected patients with moderate essential hypertension. Mean blood pressure fell by 14.5% at the maximum dose given, and this fall was significantly correlated with the initial plasma renin activity. The main fall in blood pressure occurred two hours after the first dose of captopril. These results suggest that captopril effectively lowers blood pressure in patients with essential hypertension and that the renin-angiotensin aldosterone system may maintain blood pressure in essential hypertension. This does not necessarily imply that the renin-angiotensin system is the cause of the high blood pressure.

Contrasting associations between aldosterone synthase gene polymorphisms and essential hypertension in blacks and in whites.

Background Genetic variability in the gene for aldosterone synthase – a key enzyme in the production of aldosterone – can affect sodium homeostasis and thereby blood pressure. The possibility of impaired aldosterone production for the development of hypertension is of particular relevance in black Afro-Caribbeans exposed to a high dietary sodium intake. Objectives To compare the frequency of three variants (−344C/T, intron 2 conversion, and the K173R polymorphism) of the aldosterone synthase gene in blacks and whites, and to determine any association of the variants with hypertension. Design and methods We made case–control comparisons of the three gene variants in relation to ethnic background and to essential hypertension in 193 white (51% hypertensive) and 245 black individuals (59% hypertensive) living in south London. Results The frequency of each of the variants was significantly different between the two ethnic groups. The T and the K alleles were more frequent in the black participants (79 compared with 50% for the −344T allele and 81 compared with 50% for K173 allele), whereas the frequency of the intron 2 conversion allele was much lower in that group (8 compared with 38%). None of these variants was associated with essential hypertension in the black participants. In contrast, in the white participants there was a significant and graded association between the intron 2 conversion allele and essential hypertension (odds ratio 1.86, 95% confidence interval 1.16 to 2.98; P = 0.01). Moreover, among the white population, the presence of homozygosity both of the T allele and of the intron 2 conversion alleles was associated with a much greater frequency of hypertension (71 compared with 43%; χ2 P = 0.03). Conclusions The contrasting associations between these variants and essential hypertension do not necessarily exclude the possibility that other, as yet undefined, variants of the aldosterone synthase gene could be linked with hypertension in black people. Nonetheless, the strong association between the intron 2 conversion allele and essential hypertension in the white population reinforces the view that the increased blood pressure may be due, at least in part, to abnormal expression of enzymes involved in the metabolism of adrenal mineralocorticoids.

Captopril: Contrasting Effects of Adding Hydrochlorothiazide, Propranolol, or Nifedipine

Because captopril alone does not control blood pressure in all patients with essential hypertension, studies were performed to assess the effect of sodium intake and of captopril combined with hydrochlorothiazide, propranolol, and nifedipine. Captopril given for 5 days to normotensive subjects having high, normal, and low sodium intakes reduced blood pressure the most in those on the lowest intake; the fall correlated with that in plasma angiotensin II. When 12 patients with moderate hypertension had hydrochlorothiazide added to captopril their blood pressure fell significantly. When propranolol was added to captopril, however, there was no further fall in blood pressure. When propranolol was added to captopril and a diuretic, pressures measured 4 and 6 h after the last dose of captopril showed reduced values compared with placebo; pressures measured 2 and 12 h after did not. Nifedipine added to captopril reduced blood pressure more than either drug alone. When renin and angiotensin are low, as they may be in essential hypertension, captopril is less effective; its effectiveness should increase if sodium is restricted. Both diuretics and nifedipine increase the effectiveness of captopril; propranolol does not, although it may prolong captoprils action. Experience in patients with resistant hypertension suggests that adding nifedipine to captopril may reduce the need for diuretics, while adding captopril to nifedipine may reduce the need for beta-blockers.

Potassium channel stimulation in normal subjects and in patients with essential hypertension: an acute study with cromakalim (BRL 34915).

We studied the acute effects of the potassium channel opener cromakalim on blood pressure, the renin-angiotensin-aldosterone system and renal function in eight patients with essential hypertension and five normal subjects. In the hypertensive patients, blood pressure decreased significantly from 2 to 6 h after treatment with cromakalim 1.5 mg compared with placebo, but was unchanged in the normotensives. In both groups, the heart rate and plasma renin activity increased after the administration of cromakalim compared with placebo; however, plasma aldosterone was unchanged. There was no significant change in urinary electrolyte excretion in either group; urine flow decreased after the administration of cromakalim compared with placebo in normal subjects, but not in patients with essential hypertension. Cromakalim lowers blood pressure acutely in patients with essential hypertension but not in normotensive subjects. This may be due to a greater reflex response in the normal subjects or to specific effects of cromakalim on mechanisms causing the high blood pressure.

Evidence for increased levels of a circulating ouabainlike factor in essential hypertension.

The effect of plasma from normotensive and hypertensive subjects on the binding of [3H]ouabain on human erythrocytes was investigated. The binding of [3H]ouabain on human erythrocytes was saturable and highly specific; linear Scatchard plots indicated the presence of a single type of binding site. Human plasma decreased the binding of [3H]ouabain on its receptor to a greater extent than could be accounted for by the plasma potassium concentration. The level of this circulating ouabainlike factor (or factors) was quantitated using a radioreceptor assay. Plasma from 22 hypertensive subjects (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 90 mm Hg) displayed higher levels than that from 24 normotensive subjects; furthermore there was a positive and significant correlation (r = 0.42, n = 46, p less than 0.004) between the ouabainlike content and the individual subjects systolic blood pressure. The receptor assay described is relatively simple and should be useful for further work on the nature and clinical importance of the endogenous ouabainlike factor.

Mononuclear Leucocyte Intracellular Free Calcium - Does It Correlate With Blood Pressure?

Abnormalities of calcium binding and calcium transport in cells from hypertensive subjects or animals have been previously described. Total cell sodium is reported to be increased in white blood cells from hypertensive subjects; thus by analogy with Blausteins proposal for the vascular smooth muscle cell, mononuclear leucocyte cytosolic calcium might be increased via a reduction of the Na-Ca exchange. Using the fluorescent calcium indicator, quin 2, cytosolic calcium was measured in mononuclear leucocytes from 22 hypertensive and 19 normotensive subjects. There was no significant difference between the mononuclear leucocyte cytosolic calcium level in the two groups. Incubation of the cells with 10(-4) M ouabain reduced 86 rubidium (86Rb) uptake by 80% of the control value but failed to alter cytosolic calcium. These findings are consistent with a minimal role of the Na-Ca exchange in the mononuclear leucocyte and may explain why the cytosolic calcium was not increased in hypertension despite the previous reports of increased total cell sodium in white blood cells.

Long-Term Reduction in Sodium Balance: Possible Additional Mechanism Whereby Nifedipine Lowers Blood Pressure

OBJECTIVEnTo assess the changes in sodium excretion and sodium balance after withdrawal of long term nifedipine.nnnDESIGNnSingle blind, placebo controlled study in patients receiving fixed sodium and potassium intakes.nnnSETTINGnBlood pressure unit of a teaching hospital in south London.nnnPATIENTSnEight patients with mild to moderate uncomplicated essential hypertension who had been taking nifedipine 20 mg twice daily for at least six weeks.nnnINTERVENTIONSnWithdrawal of nifedipine and replacement with matching placebo for one week.nnnMAIN OUTCOME MEASURESnUrinary sodium excretion and cumulative sodium balance, body weight, plasma atrial natriuretic peptide concentrations, plasma renin activity and aldosterone concentrations, and blood pressure.nnnRESULTSnDuring nifedipine withdrawal there was a significant reduction in urinary sodium excretion (day 1: -62.7 mmol/24 h; 95% confidence interval -90.3 to -35.0) and each patient retained a mean of 146 (SEM 26) mmol sodium over the week of replacement with placebo. Body weight and plasma atrial natriuretic peptide concentrations increased during the placebo period and seemed to be associated with the amount of sodium retained. Systolic blood pressure rose from 157 (9) to 165 (9) mmHg (95% confidence interval of difference -7.1 to 22.1) when nifedipine was replaced with matching placebo, and the rise seemed to be related to the amount of sodium that was retained.nnnCONCLUSIONSnNifedipine causes a long term reduction in sodium balance in patients with essential hypertension. This long term effect may contribute to the mechanism whereby nifedipine lowers blood pressure.

Dose response and length of action of nifedipine capsules and tablets in patients with essential hypertension: A randomised crossover study

SummaryTwelve patients with essential hypertension on no other drug treatment were entered into a randomised crossover study of 5, 10 and 20 mg capsules of nifedipine given 3 times a day and 20 mg tablets given twice a day. Each dose was given for 2 weeks in a random order. All forms of nifedipine were effective in lowering blood pressure.However, 5 mg capsules were less effective than the 10 and 20 mg capsules or 20 mg tablets. There was little to choose between the latter. All doses of nifedipine were more effective 1 and 3 h after the dose compared to subsequent times afterwards. Indeed, as time elapsed after the last dose up to 12 h, there was a gradual increase in blood pressure. However, even at 12 h the 10, 20 mg capsules and 20 mg tablets were still causing an approximate 10% reduction in blood pressure.Nifedipine tablets are as effective as capsules though they might be longer acting, particurarly around 6 h after the last dose.

Plasma atrial natriuretic peptide in essential hypertension: effects of changes in dietary sodium.

Etude chez 12 malades atteints dhypertension essentielle non compliquee, sans traitement medicamenteux. Les taux plasmatiques du peptide sont modifies par les changements dapport en sodium, comme pour les sujets normaux, mais uniquement lors de laugmentation de lingestion de sodium. La restriction semble sans effet