Vascular Adenylate Cyclase: Role of Age and Guanine Nucleotide Activation

Abstract

Particulate adenylate cyclase activity was examined in broken cell preparations of rat aorta and mesenteric artery from 3- to 5- and 9- to 13-week-old rats. While basal adenylate cyclase activity of the mesenteric artery was 4-fold greater than aortic enzyme activity, there was no difference in enzyme activity with age. GTP and the GTP analogue, 5’-guanylylimidodiρhosphate [Gpp(NH)p] stimulated adenylate cyclase activity. Stimulation by Gpp(NH)p did not differ with age for either tissue and occurred without a detectable lag. The vasodilators, isoproterenol, 2-chloroadenosine and prostaglandin E₁, were ineffective in increasing adenylate cyclase activity, although marked stimulation was demonstrated with both sodium fluoride and Gpp(NH)p. Even in combination with Gpp(NH)p, isoproterenol did not increase particulate adenylate cyclase activity of these blood vessels; however, with intact arteries, isoproterenol (10^–7 M) did increase aortic and mesenteric cyclic AMP levels. Isoproterenol increased cyclic AMP levels in rats of both ages, at a time when isoproterenol was less effective in maximally relaxing aortic strips from 9- to 13-week-old rats. These data indicate that diminished aortic relaxation with age is not associated with a reduced ability of vascular relaxants to increase aortic cyclic AMP levels. Furthermore, as a first step in establishing that guanine nucleotides are regulators of vascular adenylate cyclase, both GTP and Gpp(NH)p were found to be potent activators of adenylate cyclase from blood vessels.