The alpha(2)-adrenergic receptors in hypertension and heart failure: experimental and clinical studies

This is a brief overview of experimental and clinical studies exploring the hemodynamic functions of the alpha (2A) and alpha (2B) adrenergic receptor (AR) subtypes in animals submitted to genetic manipulations or gene treatm ent, as well as the clinical effects of central sympathetic suppression wit h the alpha (2)-AR agonist clonidine in patients with ischemic heart diseas e and/or heart failure. The animal experiments have led us to conclude that the sympathetic outflow is regulated by activation of the presynaptic alph a (2A)-AR subtype, which is the predominant alpha (2)-AR subtype in the cen tral nervous system and exerts a sympathoinhibitory (hypotensive) action; o n the contrary, activation of the central alpha (2B)-AR elicits a sympathoe xcitatory response (such as seen in salt-induced hypertension, which requir es functionally intact alpha (2B)-AR). Since there are no selective pharmac ologic agents yet capable of discriminating among alpha (2)-AR subtypes, cl inical studies utilize clonidine, the central sympathetic suppressant effec t of which has been used for 35 years to treat hypertension. In small clini cal trials, clonidine was used successfully for treatment of acute or chron ic heart failure, acute myocardial infarct or hypertensive cardiomyopathy w ith subclinical diastolic dysfunction. We speculate that future development of agents capable of selectively activating the alpha (2A)-AR or blocking the alpha (2B)-AR may further improve our capability to treat hypertension, ischemic heart disease and heart failure. J Hypertens 19:2115-2124 (C) 200 1 Lippincott Williams & Wilkins.