EFFECT OF CAPTOPRIL AND ENALAPRIL ON ENDOTHELIAL FUNCTION IN HYPERTENSIVE PATIENTS

Endothelium-dependent vasodilation is impaired in patients with essential hypertension. The objective of this study was to determine whether long-term treatment with angiotensin-converting enzyme inhibitors improves endothelium-dependent vasodilation in forearm resistance vessels of patients with hypertension. Furthermore, since tissue thiols may be relevant to nitric oxide-mediated vasodilation, we queried whether an angiotensin-converting enzyme inhibitor with a sulfhydryl group preferentially augments endothelium-dependent vasodilation in these individuals. The study included 24 patients with essential hypertension (mean age, 45+/-2 years) and 20 normotensive subjects (mean age, 47+/-1 years). Methacholine chloride (0.3 to 10 mu g/min) was infused via the brachial artery to assess endothelium-dependent vasodilation in forearm resistance vessels. Nitroglycerin (1 to 30 mu g/min) was administered to evaluate endothelium-independent vasodilation. Forearm blood flow was determined by venous occlusion strain-gauge plethysmography. Forearm vascular function studies were performed in hypertensive patients before and 7 to 8 weeks after randomization to either captopril or enalapril, angiotensin-converting enzyme inhibitors with and without a sulfhydryl moiety, respectively. Normotensive subjects were studied on only one occasion. Before treatment, the forearm vasodilative response to methacholine was attenuated in hypertensive compared with normotensive subjects (P<.01). The effects of nitroglycerin on forearm blood flow did not differ significantly between the two groups. Both captopril and enalapril reduced mean blood pressure in the hypertensive subjects (12+/-2 versus 15+/-3 mm Hg, respectively; P=NS). The forearm vasodilative response to methacholine was the same during the placebo and captopril treatment periods (P=NS) and also during placebo and enalapril treatment periods (P=NS). Even when combining both treatment groups (captopril and enalapril), no significant difference in the response to methacholine was found between placebo and drug treatment periods. It is concluded that endothelium-dependent vasodilation is abnormal in forearm resistance vessels in patients with essential hypertension, thus confirming observations made previously by others. The new finding is that antihypertensive therapy for up to 7 to 8 weeks with an angiotensin-converting enzyme inhibitor does not improve endothelium-dependent vasodilation in hypertensive humans, regardless of whether or not a sulfhydryl group is present.