[Role of endothelin in arterial hypertension. From agonists to antagonists]

Mediators synthesized or transformed in the vascular endothelium play an important role in modulating vessel tone and structure. The subsequent increase in peripheral resistance focuses attention on the hypothesis that endothelin, due to its vasoconstrictive effect and proliferative action, plays a role in hypertension. Use of converting enzyme inhibitors and endothelin receptor antagonists in normotensive subjects has confirmed the modulating effect of endothelin on vascular tone. However, these antagonists have not been found to have a major anti-hypertensive effect in hypertension. In animal models these antagonists reduce blood pressure only in case of vascular hypertrophy associated with over-production of endogenous endothelin. Current research suggests that endothelin antagonists could have a beneficial effect in certain forms of hypertension involving mineralocorticoids, angiotensin II or renal failure. Use of endothelin antagonists for hypertension will thus remain empirical until the stimulus for endogenous overexpression of vascular endothelin (angiotensin II would be a good candidate) has been identified.