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

Abstract

Abstract. 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.

Comparison of blood pro/antioxidant levels before and after acute exercise in athletes and non-athletes

“…The rise of NO (NO 2 -) levels in non-athletes may be explained by effects of shear stress, while the response of athletes may be explained by endothelium preconditioning achieved by chronic exposure to shear stress during exercise trainings and i.e. structural and functional adaptations of endothelium (Kingwell 2000;Tinken et al 2008;Bauer and Sotnikova 2010). It seems that the effects of chronic exercise on the basal NO production are more important than effects of NO production on tolerance of physical activity.…”

Gasotransmitters in Vascular Complications of Diabetes

“…Neuronal NOS (nNOS), present in neurons and skeletal muscle cells, is important for neuronal cell-cell interactions (20). NO acts as a vasodilator and inhibits platelet aggregation and stabilizes atherosclerotic plaques (21). In humans, NO-dependent vasodilatation is impaired in patients with type 2 diabetes, and lower eNOS expression and reduced NO production are the suggested underlying cause (22,23).…”

Serum Heat Shock Protein 90 Alpha: A New Marker of Hypertension-Induced Endothelial Injury?

“…The expression of eNOS is altered in many cardiovascular diseases, including hypertension, atherosclerosis, and diabetes mellitus [4]. The enzyme's activity is regulated through its interactions with such protective proteins as the 90 kDa heat shock protein (Hsp-90) and caveolin-1 [1].…”