Working under pressure: the vascular endothelium in arterial hypertension

The vascular endothelium synthesizes and releases a spectrum of vasoactive substances like nitric oxide (NO) and endothelin (ET). In hypertension, the delicate balance of endothelium-derived factors is disturbed. ET acts as t he natural counterpart to endothelium-derived NO, which exerts vasodilating , antithrombotic, and antiproliferative effects, and inhibits leukocyte-adh esion to the vascular wall. Besides its blood pressure rising effect also i n man, ET induces vascular and myocardial hypertrophy, which are independen t risk factors for cardiovascular morbidity and mortality. The derangement of endothelial function in hypertension is likely to be caused in part by g enetic factors, but also due to elevated blood pressure itself. Due to its position between blood pressure and smooth muscle cells responsible for per ipheral resistance, the endothelium is thought to be both target and mediat or of arterial hypertension. Oxidative stress plays an important role in th e pathogenesis of hypertension. Superoxide anions, ie, oxygen radicals prod uced in part by angiotensin II-activated NAD(P)H oxidase, can scavenge NO t o form peroxynitrite, which can nitrosylate membrane proteins and oxidize l ipids. Another source of superoxide is cyclooxygenase. Paradoxically, dysfu nctional endothelial NO synthase may also be a source of superoxide anions. Surprisingly and in contrast to animal experiments, not all antihypertensi ve treatments consistently restore endothelium-dependent vasodilation in pa tients with arterial hypertension. Endothelial dysfunction in hypertension is crucial both for the development of the disease process in the vasculatu re and an important therapeutic target.