Abnormal Endothelium-Dependent Vascular Relaxation in Patients with Essential Hypertension

TLDR

Endothelium controls vascular tone by modulating smooth muscle activity, and its dysfunction has been observed in atherosclerotic and hypertensive models. The study aimed to assess whether essential hypertension patients exhibit impaired endothelium‑dependent vascular relaxation by comparing forearm responses to acetylcholine and sodium nitroprusside with healthy controls. Forearm blood flow responses to graded acetylcholine and sodium nitroprusside were measured by strain‑gauge plethysmography, and acetylcholine effects were also evaluated under alpha‑adrenergic blockade with phentolamine. Hypertensive patients showed markedly reduced acetylcholine‑induced forearm vasodilation and resistance‑flow responses, while sodium nitroprusside responses were unchanged, indicating impaired endothelium‑mediated vasodilation that may underlie resistance‑vessel dysfunction.

Abstract

Endothelium regulates vascular tone by influencing the contractile activity of vascular smooth muscle. This regulatory effect of the endothelium on blood vessels has been shown to be impaired in atherosclerotic arteries in humans and animals and in animal models of hypertension.To determine whether patients with essential hypertension have an endothelium-dependent abnormality in vascular relaxation, we studied the response of the forearm vasculature to acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (a direct dilator of smooth muscle) in 18 hypertensive patients (mean age [+/- SD], 50.7 +/- 10 years; 10 men and 8 women) two weeks after the withdrawal of antihypertensive medications and in 18 normal controls (mean age, 49.9 +/- 9; 9 men and 9 women). The drugs were infused at increasing concentrations into the brachial artery, and the response in forearm blood flow was measured by strain-gauge plethysmography.The basal forearm blood flow was similar in the patients and controls (mean +/- SD, 3.4 +/- 1.3 and 3.7 +/- 0.8 ml per minute per 100 ml of forearm tissue, respectively; P not significant). The responses of blood flow and vascular resistance to acetylcholine were significantly reduced in the hypertensive patients (P less than 0.0001); maximal forearm flow was 9.1 +/- 5 ml per minute per 100 ml in the patients and 20.0 +/- 8 ml per minute per 100 ml in the controls (P less than 0.0002). However, there were no significant differences between groups in the responses of blood flow and vascular resistance to sodium nitroprusside. Because the vasodilator effect of acetylcholine might also be due to presynaptic inhibition of the release of norepinephrine by adrenergic nerve terminals, the effect of acetylcholine was assessed during phentolamine-induced alpha-adrenergic blockade. Under these conditions, it was also evident that the responses to acetylcholine were significantly blunted in the hypertensive patients (P less than 0.03).Endothelium-mediated vasodilation is impaired in patients with essential hypertension. This defect may play an important part in the functional abnormalities of resistance vessels that are observed in hypertensive patients.