Altered renal alpha-adrenoceptor regulation in DOCA-salt rats: chronic effects of alpha 1- and alpha 2-receptor blockers.

Effects on the alpha-adrenoceptor binding in the kidneys of DOCA-salt rats were examined after a 6 week treatment of once-daily injections of prazosin, a selective alpha 1-adrenoceptor blocker; yohimbine, a selective antagonist for alpha 2-adrenoceptors; and prazosin plus yohimbine. alpha 1-Receptor binding was decreased by prazosin, while alpha 2-receptor binding was increased by simultaneous administration of prazosin + yohimbine. Equilibrium dissociation constants (KD) for [3H]prazosin and [3H]yohimbine were not significantly different (between groups). Since these drugs can prevent the development of hypertension in DOCA-salt rats, the present data strongly suggests that selective alteration of alpha-receptor-mediated physiological responses is unrelated to decreased or increased binding site densities. The mechanism of hypertension prevention may involve changes in the coupling of receptors to postreceptor events.