[Endothelial dysfunction and vascular pathology].
Endothelium-dependent relaxations are due to the release by the endothelial cells of potent vasodilator substances. The best characterized endothelium-derived relaxing factor (EDRF) is nitric oxide (NO), from 1-arginine by the constitutive endothelial NO synthase. In arterial smooth muscle, NO stimulates soluble guanylate cyclase which leads to the accumulation of cyclic GMP. Endothelial cells also release substances (EDHF) that hyperpolarize vascular smooth muscle. The release of NO from the endothelium can be mediated by both Gi (catecholamines, serotonin, thrombin) and Gq (adenosine diphosphate, bradykinin) G-proteins. In arteries with regenerated endothelium and/or atherosclerosis, there is a selective loss of the Gi mechanism of No-release which favours the occurrence of vasospasm, thrombosis and cellular growth. In addition to relaxing factors, the endothelial cells can produce contracting-substances (EDCF) which include superoxide anions, endoperoxides, thromboxane A2 and endothelin-1. The propensity to release EDCFs is maintained or even augmented in diseased blood vessels. The switch from a normally predominant release of NO to that of EDCF may play a crucial role in vascular disease.
Vanhoutte
P M
PM
Department of Pharmacology, Li Ka Shin Faculty of Medicine, The University of Hong Kong.
D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology; D001808:Blood Vessels / Q000473:pathology / Q000503:physiopathology*; D018450:Disease Progression; D016232:Endothelins / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D045462:Endothelium-Dependent Relaxing Factors / Q000502:physiology; D006706:Homeostasis; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000502:physiology; D018384:Oxidative Stress; D010974:Platelet Aggregation / Q000502:physiology; D012038:Regeneration; D012307:Risk Factors; D015398:Signal Transduction; D013927:Thrombosis / Q000473:pathology / Q000503:physiopathology; D014652:Vascular Diseases / Q000473:pathology / Q000503:physiopathology*
D016232:Endothelins; D045462:Endothelium-Dependent Relaxing Factors; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III