Clinical importance of coronary endothelial vasodilator dysfunction and therapeutic options - Introduction

The vascular endothelium plays a key role in the control of vasomotor tone, local haemostasis and vascular wall proliferation processes. These respons es are mediated by a variety of substances released from the endothelium in response to physiological stimuli, including prostacyclin, endothelin, and most importantly nitric oxide (NO). NO mediates vasodilation and furthermo re inhibits platelet aggregation, expression of adhesion molecules for mono cytes and adhesion of neutrophils, and it impairs growth of vascular smooth muscle cells, Risk factors for coronary atherosclerosis, such as hyperchol esterolaemia, impair NO bioactivity, mainly due to an oxidative stress by s uperoxide radicals (O-2(-)), which are able of rapidly inactivating endothe lium-derived NO. Impaired NO bioactivity leads to unopposed paradoxical vas oconstriction of epicardial conductance vessels in response to physiologica l stimuli such as sympathetic activation as well as impaired vasodilator fu nction of coronary resistance vessels. Therefore, endothelial dysfunction c ontributes to ischaemic manifestation of coronary artery disease. In additi on, enhanced paradoxical vasoconstriction and a loss of endothelial antithr ombotic activities might unfavourably modulate the course of acute coronary syndromes. Thus, the aim of therapeutic interventions is to increase NO bi oavailability by either increasing NO production or decreasing O-2(-) produ ction in the endothelium. This goal can be reached, for example by ACE inhi bitors, lipid-lowering drugs, increased shear-stress by physical exercise, oestrogens, and L-arginine, which have already been shown to improve endoth elial vasodilator function, Nevertheless, it has to be determined whether a meliorated endothelial function will contribute to improved patients progno sis.