Abstract :
The endothelium plays a pivotal role in a number of responses (relaxations or contractions) of isolated arteries and veins from animals and humans. The endothelium-dependent relaxations are due to the release by the endothelial cells of potent nonprostanoid vasodilator substances. Among these, the best characterized is endothelium-derived relaxing factor (EDRF) which most likely is nitric oxide (NO). Nitric oxide is formed by the metabolism of l-arginine by the enzyme NO synthase in the endothelial cells. In arterial smooth muscle, the relaxations evoked by EDRF are explained best by the stimulation by NO of soluble guanylate cyclase that leads to the accumulation of cyclic GMP. In a number of animal blood vessels, the endothelial cells release a substance that causes hyperpolarization of the cell membrane (endothelium-derived hyperpolarizing factor, EDHF). In blood vessels from hypertensive animals, endothelium-dependent relaxation usually are reduced. A decreased release of EDRF and/or a reduced sensitivity of vascular smooth muscle to NO can contribute to the reduction. The limited information available on isolated human blood vessels, or obtained in situ in human limbs, concur with the conclusions reached with isolated animal tissues. In addition to relaxing factors, the endothelial cells can produce contracting substances (endothelium-derived contracting factors; EDCFs) which include superoxide anions, endoperoxide, thromboxane A2 and the potent vasoconstrictor peptide endothelin. To judge from animal studies, the propensity to release EDCFs is maintained or even augmented in diseased blood vessels. This is particularly the case in arteries taken from spontaneously hypertensive animals, where the release of endothelium-derived endoperoxide(s) is increased, and the sensitivity of the vascular smooth muscle to the EDCF is augmented. The switch from a normally predominant release of EDRF to that of EDCFs may play a crucial role in the vascular hyperreactivity seen in hypertension.
