Endothelin plasma levels in hypertensive patients with vascular disease

Physiology of endothelin: Circulating levels of immunoreactive endothelin-1 are very low, and below the level required for vaso-activity. It has a long duration of action but only 1-2 min of half-life. It is metabolized in the lungs, liver and kidney and is a profound constrictor of the pulmonary, renal, coronary and peripheral circulation. The prepro-endothelin-1 promoter contains an insulin-responsive element. Inhibitory regulators include nitric oxide and prostacyclin. Endothelin in hypertension and cardiovascular disease: In both experimental animal and human hypertension, endothelin levels are not consistently reported to be elevated. They are, however, elevated in atherosclerosis, congestive cardiac failure and renal insufficiency. Since endothelin is a sensitive marker of endothelial injury, these elevated levels may simply reflect diffuse endothelial injury. The endothelium is a crucial factor in cardiovascular disease. Three important risk factors, ageing, hypertension and hypercholesterolaemia, are associated with a decreased basal and stimulated release of endothelium-derived nitric oxide. The release of endothelin-1 appears to increase with age while sensitivity to this peptide decreases.

Endothelin may be a useful marker of end-organ damage, for example in atherosclerosis, but its pathogenic effects in hypertension remain unclear.