Endothelium-derived nitric oxide: the endogenous nitrovasodilator in the human cardiovascular system.
The L-arginine pathway within endothelial cells in the blood vessel wall is the source of production of the endogenous nitrovasodilator, nitric oxide (NO). NO is released under basal conditions and in response to various stimuli such as shear stress and in response to platelet-derived products, coagulation factors and hormones. NO is the mediator of endothelium-dependent relaxation in the circulation and exerts its effects by activating soluble guanylyl cyclase in vascular smooth muscle, which in turn leads to the formation of cyclic guanosine monophosphate (cGMP) and to relaxation. In addition to its effects on vascular smooth muscle, NO is also released abluminally to interact with circulating platelets. Increases in cGMP in platelets are associated with a decreased adhesion and aggregation of cells. Thus, endothelium-derived NO, through its vasodilator and anti-aggregatory properties, prevents vasospasm and thrombus formation in the circulation and thereby helps to maintain blood flow to vital organs such as the heart. Therapeutic nitrates also exert their effects by releasing NO from their molecules and activating soluble guanylyl cyclase. Their effects are particularly pronounced in arteries without endothelium and are reduced in the presence of the basal formation of endothelium-derived NO in intact arteries. The lower basal formation of endothelium-derived NO in veins, as compared to arteries, contributes to the greater sensitivity of venous circulation to nitrates. Thus, the endothelial L-arginine pathway plays an important protective role in the local regulation of blood flow and through its vasodilator and antiplatelet properties.
Lüscher
T F
TF
Department of Medicine, University Hospital Basel, Switzerland.
D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009566:Nitrates / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D014664:Vasodilation / Q000502:physiology*
D009566:Nitrates; D009569:Nitric Oxide