Natriuretic and water diuretic effects of central alpha 2-adrenoceptor agonists.

Abstract

Methyldopa, clonidine, and a more recently developed drug, guanabenz, have similar antihypertensive mechanisms, predominantly suppression of central sympathetic outflow by alpha 2-receptor agonism and consequent reduction in peripheral sympathetic activity. Recent studies clearly demonstrate an important role of the sympathetic nervous system in the control of sodium excretion. Therefore, the interrelationships between the use of central alpha-adrenergic agonists as antihypertensive agents and their influence on renal handling of sodium are important. Certain problems accompany the use of the older centrally acting drugs as monotherapy. As a response to the hypotensive effects of these drugs, certain renal adaptations take place which presumably are homeostatic attempts to restore blood pressure and plasma volume to baseline, but which lead to a positive sodium balance, antihypertensive tolerance and occasionally the development of overt edema. The high incidence of tolerance has led most physicians to use diuretics on a routine basis, superimposing the side effects of diuretics and compromising compliance. The potential natriuretic properties of guanabenz appear to counter-balance the sodium retaining side effects commonly seen with other centrally acting and vasodilating antihypertensive drugs. This property, therefore, makes this agent a scientifically interesting and potentially useful therapeutic drug for the therapy of high blood pressure.