Decreased β-adrenoceptor-mediated vasodilation in aorta from aged rats: possible involvement of a stimulatory GTP-binding protean

Abstract

KCl-contracted aortic rings from 18-month-old rats, in contrast with those from 2-month-old rats, showed a substantial reduction in the relaxant effects of the non-selective β-adrenoceptor agonist, isoproterenol, and of the selective β 2-adrenoceptor agonist, clenbuterol, without changes in the relaxant actions of forskolin (an activator of the adenylate cyclase), 3-isobutyl-1-methyl-xanthine (a phosphodiesterase inhibitor) or acetylcholine (an endothelium- and cyclic GMP-dependent vasodilator). The relaxant responses induced by adenosine and 2-Cl-adenosine were also reduced in aged aortas. Isoproterenol and cholera toxin (an inhibitor of GTPase activity of the stimulatory GTP-binding protein) reduced cAMP production in aortas from 18-month-old rats. It is suggested that a decrease in the function of the stimulatory GTP-binding protein may contribute at least in part to the impairment in the vasodilation induced by activation of β-adrenoceptors in aortas from aged rats.