Invited Controversy Is Endothelin Involved in the Pathogenesis of Hypertension?

Endothelins are a family of potent vasoconstrictor peptides released by endothelial cells. The production of endothelin-1 (ET-1) can be stimulated by aggregating platelets and angiotensln II. It is inhibited by increases in intracellular concentration of cyclic GMP. ET-1 causes biphasic changes in arterial blood pressure and of peripheral resistance in several vascular beds: an initial transient decrease (due to release of nitric oxide, prostacyclin, or both from the endothelium) followed by a sustained increase (mainly due to direct activation of vascular smooth muscle). The vasoconstriction induced by the peptide is inhibited by increases in cyclic GMP. Few studies, except in pregnant women with preeclampsia or eclampsia, indicate that the circulating levels of the peptide are augmented in hypertension. Likewise, the information available on changes in responsiveness to endothelins in blood vessels from hypertensive animals is controversial. Until the effect of selective antagonists on the production or action of the peptide can be determined in hypertensive patients, caution must be exerted when implying a role for endothelin in the pathophysiology of hypertension. (Hypertension 1993;21:747-751) KEY WORDS • guanosine cyclic monophosphate • endothelins • endothelium • hypertension, essential • preeclampsia • muscle, smooth, vascular The endothelium can release both dilator (endo-thelium-derived relaxing factor [EDRF, mostlikely nitric oxide], endothelium-derived hyper