Endothelial dysfunction in hypertension. A critical evaluation.

Abstract

It has been proposed repeatedly that essential hypertension as well as secondary hypertension is associated in a causative manner with endothelial dysfunction in the resistance vessels. Endothelial damage and dysfunction may be expected to attenuate the endogenous vasodilator mechanism of EDRF (nitric oxide) and hence cause a rise in blood pressure. This attractive hypothesis, put forward a few years ago, is subject to considerable debate at present. In the present survey the arguments in favour and against this hypothesis are critically discussed. The following arguments support the causative association between endothelial dysfunction: the hypertensive effect of NO-synthase blockade by L-NAME and related agents; the antihypertensive effect of L-arginine in salt-loaded Dahl rats; the impaired vasodilator effect in the forearm vascular bed of hypertensives; diminished NO-synthesis in hypertensives. However, several findings speak against the association between hypertensive disease and endothelial dysfunction. For instance: no clear demonstration of impaired endothelial function in isolated vessels of hypertensive patients and animals; studies in the human forearm vascular bed where endothelial function appears to be fully intact in hypertensives. Attempts are made to explain the discrepancies between the various findings. So far the association between endothelial dysfunction and hypertension appears to be an uncertain one.