Effect of potassium on vasodilation to acetylcholine in essential hypertension.

Patients with essential hypertension show impaired endothelium-dependent vasodilation induced by acetylcholine. Because dietary potassium supplementation increases endothelium-dependent relaxations to acetylcholine in hypertensive rats, we designed the present study to investigate whether potassium increases endothelium-dependent vasodilation in essential hypertensive patients. Therefore, in patients with essential hypertension (n=13) and in normotensive control subjects (n=13) we evaluated the effect of intrabrachial potassium chloride (0.2 mmol/min) on forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 μg/100 mL forearm tissue per minute). In both groups of patients, potassium chloride infusion augmented local plasma potassium concentrations. Furthermore, in essential hypertensive patients but not in normotensive subjects it increased the vasodilating effect of the first three infusion rates of acetylcholine. In contrast, in seven adjunctive essential hypertensive patients, potassium chloride did not alter intrabrachial sodium nitroprusside-induced forearm vasodilation (1, 2, and 4 μg/100 mL forearm tissue per minute). Finally, to evaluate the role of nitric oxide on potassium-dependent facilitation of acetylcholine-induced vasodilation in essential hypertension, we studied the effect of intrabrachial N(G)-monomethyl L-arginine (100 μg/100 mL per minute) in another group of seven hypertensive patients. Vasodilation to acetylcholine was again increased by potassium chloride; N(G)-monomethyl L-arginine slightly blunted the vasorelaxing effect of acetylcholine but abolished the potentiating effect of potassium. These results indicate that potassium increases endothelium-dependent vasodilation to acetylcholine in essential hypertensive patients but not in normotensive control subjects throughout the nitric oxide pathway and suggest that this effect might be a mechanism accounting for the beneficial effects proposed for potassium in essential hypertension

Lack of correlation between microalbuminuria and endothelial function in essential hypertensive patients.

Objective: To evaluate whether microalbuminuria, defined as urinary albumin excretion between 30 and 300 mg/24 h, is associated with endothelial dysfunction in essential hypertensive patients. Design: We correlated urinary albumin excretion with vasodilatation in response to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) agonists in the forearm vascular bed in essential hypertensive patients with (n = 13) and without (n = 23) microalbuminuria and matched normotensive controls (n = 21). Method: We studied forearm vascular responses (strain-gauge plethysmography) to intrabrachial infusion of acetylcholine (0.15, 0.45, 1.5, 4.5 and 15 ng/100 ml forearm tissue/min) and of sodium nitroprusside (1, 2, 4 ng/100 ml forearm tissue per min). Minimal forearm vascular resistances (the ratio between mean arterial pressure and maximal forearm vasodilatation induced by 13 min of ischaemia + 1 min of exercise) were also evaluated. Results: Responses to acetylcholine, but not to sodium nitroprusside, were significantly blunted and minimal forearm vascular resistances were increased in hypertensive patients compared with controls. However, no correlation was found between urinary albumin excretion and vasodilatation in response to acetylcholine or to sodium nitroprusside or between urinary albumin excretion and minimal forearm vascular resistances. Conclusions: In hypertensive patients, increased urinary albumin excretion is associated neither with functional nor with structural dysfunction in the forearm vasculature

Menopause is associated with endothelial dysfunction in women

To evaluate the effect of endogenous estrogens on endothelial function in humans, we examined whether menopause is associated with impairment in endothelium-dependent vasodilation in normotensive and essential hypertensive women. In 73 normotensive subjects (37 women, 36 men) and 73 hypertensive patients (36 women, 37 men), we studied endothelial function by measuring forearm blood flow modifications (strain-gauge plethysmography) induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 mu g/100 mL per minute), an endothelium-dependent vasodilator, and sodium nitroprusside (1, 2, and 4 mu g/100 mL per minute), an endothelium-independent vasodilator. Women younger than 45 years had normal menstrual cycles. In essential hypertensive patients, responses to acetylcholine but not to sodium nitroprusside were significantly (P<.001) reduced compared with responses in normotensive subjects. Moreover, in both groups, vasodilation to acetylcholine showed a marked negative correlation with advancing age (normotensive subjects: r=-.88, P<.001; hypertensive patients: r=-.87, P<.001). In contrast, vasodilation to sodium nitroprusside showed a less evident negative correlation with advancing age (normotensive subjects: r=-.46, P<.01; hypertensive patients: r=-.48, P<.01). However, in normally menstruating normotensive women, no endothelial dysfunction was observed, and age-related impairment in endothelium-dependent vasodilation was evident only after menopause, In normally menstruating hypertensive women, aging was associated with endothelial dysfunction although the deterioration of endothelium-dependent vasodilation was less marked than that in men. In contrast, after menopause, the age-related endothelial dysfunction in hypertensive women was similar to that observed in men. Finally, no sex-related difference in the response to sodium nitroprusside was observed in either normotensive subjects or essential hypertensive patients. Age-related endothelial dysfunction is attenuated in premenopausal normotensive and hypertensive women compared with men, whereas no sex-induced difference is observed after menopause, suggesting a protective effect of endogenous estrogens on endothelial function

Aging and endothelial function in normotensive subjects and patients with essential hypertension

Experimental data from normotensive and hypertensive animals indicate that aging is associated with impaired endothelium-dependent relaxations to acetylcholine, and this possibility appears to be confirmed in the human coronary artery. In the present study, we evaluated the effect of age on endothelial responsiveness in the forearm vessels of either normotensive control subjects or essential hypertensive patients

Humoral and haemodynamic effects of idrapril calcium, the prototype of a new class of ACE-inhibitors, in essential hypertensive patients.

Idrapril is the prototype of a new class of ACE inhibitors, characterised by the presence of a hydroxdmic group. Six untreated in-patients with essential hypertension were given single oral doses of the calcium salt of idrapril, idrapril calcium (200 mg) and placebo according to a double blind, randomised experimental design. Supine and upright blood pressure, heart rate, plasma idrapril serum ACE, active renin and angiotensin II were measured at timed intervals for 24 hours after dosing. Plasma idrapril reached a peak after 2 hours (3.01 mu g . ml(-1)), and by 12 hours the compound had al most disappeared (67 ng . ml(-1)). Derived t(1/2) was 1.4-2.2 h. ACE activity was suppressed [from 77.9 to 3.3 after 2 hours and 11.8 after 12 hours nmol(-1). min(-1). ml] and angiotensin II production inhibited [from 8.8 to 3.1 (after 1 hour) and 7.5 (after 12 hours) pg . ml(-1)] for up to 12 h, while active renin rose up to 24 h [from 12.3 to 20.1 (after 8 hours) and 17.5 (after 24 hours) pg ml(-1)]. Compared to placebo, idrapril calcium significantly lowered both supine blood pressure starting at 4 hours (idrapril calcium 140/93 mmHg; placebo 157/101 mmHg) up to 24 hours (idrapril calcium 142/91 mmHg; placebo: 155/97 mmHg), and upright blood pressure starting at 3 hours (idrapril calcium 135/95 mmHg; placebo 147/100 mmHg) up to 24 hours (idrapril calcium 132/92 mmHg; placebo 145/100 mmHg). Idrapril calcium appears to be an effective ACE inhibitor in essential hypertension, with a hypotensive action for up to 24 h