ABNORMAL ENDOTHELIUM-DEPENDENT VASCULAR RELAXATION IN PATIENTS WITH ESSENTIAL-HYPERTENSION

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 endotheliumdependent 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<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<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 α-adrenergic blockade. Under these conditions, it was also evident that the responses to acetylcholine were significantly blunted in the hypertensive patients (P<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. The importance of the endothelium in modulating the activity of vascular smooth muscle and therefore in regulating vascular tone was first suggested by the pioneering studies of Furchgott and Zawadzki.1 These authors reported that the damage or absence of endothelial cells curtails the vasodilator action of acetylcholine and other substances2 that is normally observed when the endothelium is intact. Endothelium-depcndent relaxation has subsequently been shown to occur in most mammalian species,2 and has also been demonstrated in humans by in vitro studies using arterial preparations.3 4 5 More recently, studies in normal humans have confirmed these observations and have indicated that this… © 1990, Massachusetts Medical Society. All rights reserved.