The α2-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 treatment, as well as the clinical effects of central sympathetic suppression with the alpha (2)-AR agonist clonidine in patients with ischemic heart disease and/or heart failure. The animal experiments have led us to conclude that the sympathetic outflow is regulated by activation of the presynaptic alpha (2A)-AR subtype, which is the predominant alpha (2)-AR subtype in the central nervous system and exerts a sympathoinhibitory (hypotensive) action; on the contrary, activation of the central alpha (2B)-AR elicits a sympathoexcitatory response (such as seen in salt-induced hypertension, which requires functionally intact alpha (2B)-AR). Since there are no selective pharmacologic agents yet capable of discriminating among alpha (2)-AR subtypes, clinical studies utilize clonidine, the central sympathetic suppressant effect of which has been used for 35 years to treat hypertension. In small clinical trials, clonidine was used successfully for treatment of acute or chronic heart failure, acute myocardial infarct or hypertensive cardiomyopathy with 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) 2001 Lippincott Williams & Wilkins.