In the last thirty years, it became obvious that the endothelium mediates relaxations of the underlying vas- cular smooth muscle cells by releasing endothelium-derived relaxing factors （EDtlF） , which results in end...
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In the last thirty years, it became obvious that the endothelium mediates relaxations of the underlying vas- cular smooth muscle cells by releasing endothelium-derived relaxing factors （EDtlF） , which results in endothelium- dependent vasodilatations. The best characterized EDRF is nitric oxide （NO） formed from 1-arginine by the consti- tutive endothelial NO synthase （eNOS）. NO diffuses to the vascular smooth muscle where it stimulates soluble gua- nylyl cyclase with, under normal conditions, the resulting production of cyclic C, MP. The release of NO from the endothelium can be mediated by both pertussis toxin-sensitive C,i- （ e. g. α2-adrenergic agonists, serotonin） and in- sensitive C,q- （adenosine diphosphate, bradykinin） proteins. The ability of the endothelial cell to release relaxing factors can be up-regulated by estrogens, increased flow, exercise, diet （ ω3-unsaturated fatty acids, polyphenols） and antioxidants, and down-regulated by oxidative stress and increased presence of oxidized low density lipoproteins （LDL）. It is reduced chronically by aging, smoking, environmental pollution and in hypertension and diabetes. Following injury or apoptotic death, the endothelium regenerates. However, in regenerated endothelial cells, there is an early selective loss of the pertussis-toxin sensitive mechanisms of EDRF-release. The reduced release of NO resulting from the endothelial dysfunction in regenerated areas sets the stage for the occurrence of vasospasm and thrombosis as well as it permits the inflammatory response leading to atherosclerosis. In addition to causing less di- rect relaxation of the underlying vascular smooth muscle, reduced release of NO also unleashes the production of vasoconstrictor prostanoids and/or endothelin-1. Blunted endothelium-dependent relaxations can also be caused by unresponsiveness of the vascular smooth muscle to NO. Finally, in coronary arteries hypoxia causes an acute aug- mentation of vasoconstrictor responses that is depend
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