Nitric oxide--the endothelium-derived relaxing factor and its role in endothelial functions.

Vascular endothelium plays a key role in the local regulation of vascular tone and vascular architecture by release of vasodilator and vasoconstrictor substances, as well as factors with pro-coagulant, anticoagulant, fibrinolytic, antibacterial properties, growth factors, chemokines, free radicals, etc. Release of endothelium-derived relaxing factors such as nitric oxide (NO), prostaglandins and endothelium-derived hyperpolarizing factor, as well as vasoconstricting factors such as endothelin, superoxide and thromboxanes play an influential role in the maintenance and regulation of vascular tone and the corresponding peripheral vascular resistance. Under physiological conditions, the release of anticoagulant and smooth muscle relaxing factors exceeds the release of other substances. The first part of this review presents the functions of the endothelium itself, the nature of the endothelium-derived relaxing factor, its production by NO synthases, mechanisms of its action via activation of soluble guanylyl cyclase and production of cyclic 3'-5'-guanosine monophosphate. The resulting biological effects include vasodilatation, regulation of vessel wall structure, increased regional blood perfusion, lowering of systemic blood pressure, antithrombosis and antiatherosclerosis effects, which counteract the vascular actions of endogenous vasoconstrictor substances. Impaired endothelial function, either as a consequence of reduced production/release or increased inactivation of endothelium-derived vasodilators, as well as interactions of NO with angiotensin, reactive oxygen species and oxidized lipoproteins, has detrimental functional consequences and is one of the most important cardiovascular risk factors. Therefore the second part of this review assesses the pathophysiologic impact of the endothelium in examples of cardiovascular pathologies, e.g. endotheliopathies caused by increased angiotensin production, lipid peroxidation, ischemia/reperfusion or diabetes.