A role for endothelin in the pathogenesis of hypertension: fact or fiction?

Endothelin-1 (ET-1) was discovered 10 years ago. Because it is one of the most potent vasoconstrictors in vivo, a pathophysiological role for the peptide as a mediator of hypertension has been postulated. Several clinical studies, however, have been unable to identify elevated ET levels in the plasma of hypertensive patients, suggesting that it does not play a prominent role in this disease. More recently, evidence has been presented that ETs act predominantly at the autocrine/paracrine level and that measurements of plasma levels can give only an indirect view of the activity of the system. In addition, transgenic technology has uncovered new actions of the peptide systems in recent years, which point to a key function of the system in prenatal development. Moreover, investigation of conditions associated with hypertensive end-organ damage, such as chronic renal failure, has led to a re-evaluation of the role of the ET system in hypertension. This article discusses this recent evidence and defines the exact role of the ET system in hypertension and hypertensive end-organ damage.