EFFECT OF CAPTOPRIL AND ENALAPRIL ON ENDOTHELIAL FUNCTION IN HYPERTENSIVE PATIENTS

Endothelium-dependent vasodilation is impaired in patients with essent ial hypertension. The objective of this study was to determine whether long-term treatment with angiotensin-converting enzyme inhibitors imp roves endothelium-dependent vasodilation in forearm resistance vessels of patients with hypertension. Furthermore, since tissue thiols may b e relevant to nitric oxide-mediated vasodilation, we queried whether a n angiotensin-converting enzyme inhibitor with a sulfhydryl group pref erentially augments endothelium-dependent vasodilation in these indivi duals. The study included 24 patients with essential hypertension (mea n age, 45+/-2 years) and 20 normotensive subjects (mean age, 47+/-1 ye ars). Methacholine chloride (0.3 to 10 mu g/min) was infused via the b rachial 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. Forea rm vascular function studies were performed in hypertensive patients b efore and 7 to 8 weeks after randomization to either captopril or enal april, angiotensin-converting enzyme inhibitors with and without a sul fhydryl moiety, respectively. Normotensive subjects were studied on on ly one occasion. Before treatment, the forearm vasodilative response t o methacholine was attenuated in hypertensive compared with normotensi ve subjects (P<.01). The effects of nitroglycerin on forearm blood flo w 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 vasodil ative response to methacholine was the same during the placebo and cap topril treatment periods (P=NS) and also during placebo and enalapril treatment periods (P=NS). Even when combining both treatment groups (c aptopril 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 fo rearm 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 angioten sin-converting enzyme inhibitor does not improve endothelium-dependent vasodilation in hypertensive humans, regardless of whether or not a s ulfhydryl group is present.