Endothelium-derived relaxing factors and converting enzyme inhibition.
Endothelial cells can produce at least 3 substances which cause relaxation of vascular smooth muscle: (1) endothelium-derived nitric oxide (NO, which is secreted not only toward the underlying vascular smooth muscle but also into the blood vessel lumen). NO also has a physiological role at the interface between the endothelial cells and the blood content; in particular, NO inhibits the adhesion of platelets and leukocytes to the endothelium. (2) Endothelium-derived hyperpolarizing factor, presumably a labile metabolite of arachidonic acid formed through the P-450 pathway, which appears to act on smooth muscle by being one of the few physiologic openers of the potassium channels. (3) Prostacyclin, which can be considered as an endothelium-derived relaxing substance, given its vasodilator activity and its primarily endothelial origin. One of the main factors modulating the release of these EDRFs is the shear stress of blood on the arterial wall, which explains why flow-induced vasodilation is endothelium-dependent in the intact organism. The peptide bradykinin is a potent stimulus for EDRF release. The normal lifespan of an adult human endothelial cell is some 30 years, after which aging takes its toll and the cells must be replaced. The regenerated cells lose some of their ability to release EDRF, in particular in response to platelet aggregation and thrombin. Finally, in hypertension and atherosclerosis, a decrease in endothelium-dependent relaxation is obvious in response to a variety of stimuli. All converting enzyme inhibitors tested so far share a potentiating effect on endothelium-dependent relaxation to bradykinin, and augmented local production of bradykinin may help to explain the acute vasodilator properties of these compounds.
D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000378:metabolism; D001685:Biological Factors / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism; D011464:Epoprostenol / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D011464:Epoprostenol; D001920:Bradykinin