Renal endothelin in hypertension

Due to the potent vasoconstrictor action of endothelin-l and its synthesis throughout the vasculature and other tissues, most investigators believe th at it is an active participant in the pathogenesis of hypertension. However , the autocrine and paracrine nature of the endothelin system has made its role difficult to define. In recent years, it has become apparent that endo thelin-l contributes to the regulation of renal salt and water excretion an d that it is a major contributor to the hypertension associated with salt-d ependency. Evidence suggests that endothelin-l within the renal medulla is activated in conditions of salt loading and inhibits reabsorption of sodium in a nitric oxide-dependent manner. Blockade of endothelin A receptors low ers arterial pressure in animal models of salt-dependent hypertension. Furt hermore, circulating levels of endothelin-l are generally higher in African -Americans compared to white Americans as is the prevalence of salt-depende nt hypertension. Therefore, if would appear that use of endothelin A-select ive receptor antagonists should be targeted to those individuals at risk fo r salt-dependent hypertension. Blockade of endothelin B receptors would not be desirable because of their important role in eliminating a salt load. C urr Opin Nephrol Hypertens 9:157-164. (C) 2000 Lippincott Williams & Wilkin s.