Endothelial dysfunction in essential hypertension.

Abstract

In the last decade, significant advances have occurred in our understanding of the presence and nature of endothelial dysfunction in a number of cardiovascular conditions, including hypertension. Endothelium-derived nitric oxide (NO) is recognized as an important mediator of endothelium-dependent vascular relaxation, and a defect in the endothelium-derived NO system--possibly decreased synthesis and/or release of NO by endothelial cells--is now known to cause the abnormal response to acetylcholine in hypertensive vessels and to account at least in part for the increased vascular resistance observed in hypertension. Extensive research by our laboratory and others to determine the nature of the defect in the NO system has found that the defect is not related to decreased availability of L-arginine, the NO precursor, or to a defect at the muscarinic receptor level or a specific G protein-dependent intracellular signal-transduction pathway; nor is it related to extracellular inactivation of NO by superoxide anion. These findings have contributed to our understanding of endothelial dysfunction in essential hypertension and have pointed out distinctions between the mechanisms leading to this vascular abnormality in hypertensive and hypercholesterolemic patients. While the exact nature of the NO system defect in hypertension is still to be clarified, the vasoconstrictive and proatherogenic effects of endothelial dysfunction probably contribute to the cardiovascular complications associated with elevated blood pressure. Continued research targeted at the identification of the precise mechanism(s) responsible for endothelial dysfunction in hypertension may lead to the development of novel therapeutic strategies to reduce the vascular complications associated with the hypertensive process.