Nitric oxide and coronary endothelial dysfunction in humans

Abstract

Time for primary review 21 days. The endothelium provides a variety of important functions involved in the cardiovascular homeostasis. The assessment of endothelial function in humans has focused primarily on endothelial dependent vasomotion in response to the release of NO. In particular, clinical studies have evaluated vasomotor tone following changes in flow or stimuli for the release of NO from the endothelium, such as acetylcholine, substance P or serotonin [1]. However, NO not only acts as a vasodilating substance but also affects other functions of the endothelium such as the adhesive properties of the endothelium with respect to the interaction with leucocytes and platelets [2]. Despite the pivotal contribution of in vitro studies for the elucidation of underlying mechanisms, the clinical implication of endothelial function can only be appreciated by studies in humans in vivo, since tissue or cells are exposed to an artificial environment i.e. lacking the neurohumoral influences present in vivo. To critically review the role of NO in coronary endothelial dysfunction in humans the present review focuses on observations made by the in vivo assessment of endothelial dependent vascular responses. In normal individuals increases in blood flow is associated with flow-dependent, endothelium-mediated vasodilation [3] which is related to the release of NO from the endothelium [4,5]. Similarly, acetylcholine, bradykinin or substance P elicit endothelium-dependent dilation of large and small vessels, which, in part, is due to the stimulated release of NO. However, the effect of acetylcholine, the most commonly used agent in the clinical setting, is composed of two divergent actions, that is, vasodilation by the stimulated release of NO and other vasodilating substances such as EDHF from the endothelium, and direct vasoconstricting effects on the underlying vascular smooth muscle, particularly with higher doses. In contrast to acetylcholine, bradykinin—and possibly substance P—is likely to … * Corresponding author. Tel.: +49-511-532-3841; fax: +49-511-532-5412 Drexler.Helmut{at}MH-Hannover.de