title: Clinical importance of coronary endothelial vasodilator dysfunction and therapeutic options.
abstract: The vascular endothelium plays a key role in the control of vasomotor tone, local haemostasis and vascular wall proliferation processes. These responses 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 furthermore inhibits platelet aggregation, expression of adhesion molecules for monocytes and adhesion of neutrophils, and it impairs growth of vascular smooth muscle cells. Risk factors for coronary atherosclerosis, such as hypercholesterolaemia, impair NO bioactivity, mainly due to an oxidative stress by superoxide radicals (O2-), which are able of rapidly inactivating endothelium-derived NO. Impaired NO bioactivity leads to unopposed paradoxical vasoconstriction of epicardial conductance vessels in response to physiological stimuli such as sympathetic activation as well as impaired vasodilator function of coronary resistance vessels. Therefore, endothelial dysfunction contributes to ischaemic manifestation of coronary artery disease. In addition, enhanced paradoxical vasoconstriction and a loss of endothelial antithrombotic activities might unfavourably modulate the course of acute coronary syndromes. Thus, the aim of therapeutic interventions is to increase NO bioavailability by either increasing NO production or decreasing O2- production in the endothelium. This goal can be reached, for example by ACE inhibitors, lipid-lowering drugs, increased shear-stress by physical exercise, oestrogens, and L-arginine, which have already been shown to improve endothelial vasodilator function. Nevertheless, it has to be determined whether ameliorated endothelial function will contribute to improved patients prognosis.
authors.affiliation: Department of Internal Medicine IV, J. W. Goethe University Frankfurt, Germany.
authors.forename: M B
authors.initials: MB
authors.lastname: Britten
authors.forename: A M
authors.initials: AM
authors.lastname: Zeiher
authors.forename: V
authors.initials: V
authors.lastname: Schächinger
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D001120:Arginine / Q000627:therapeutic use; D001161:Arteriosclerosis / Q000503:physiopathology; D003327:Coronary Disease / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D015444:Exercise; D012739:Gonadal Steroid Hormones / Q000627:therapeutic use; D006801:Humans; D006937:Hypercholesterolemia / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D012739:Gonadal Steroid Hormones; D000960:Hypolipidemic Agents; D013481:Superoxides; D009569:Nitric Oxide; D001120:Arginine