Role of adenylyl cyclase in reduced [beta]-adrenoceptor-mediated vasorelaxation during maturation

• Published in: Brazilian journal of medical and biological research 2016-07, Vol.49 (7)
• Main Authors: Lopez-Canales, O.A, Castillo-Hernandez, M.C, Vargas-Robles, H, Rios, A, Lopez-Canales, J.S, Escalante, B
• Format: Article
• Language: English
• Subjects: Adrenergic receptors; Analysis; Cardiovascular diseases; Care and treatment; Development and progression; G proteins; Gene expression; Hypertension; Phosphorylation; Risk factors; Vasodilation
• ISSN: 0100-879X
• DOI: 10.1590/1414-431X20165285

Beta-adrenergic receptor ([beta]AR)-dependent blood vessel relaxation is impaired in older animals and G protein activation has been suggested as the causative mechanism. Here, we investigated the role of [beta]AR subtypes ([beta]1AR, [beta]2AR, and [beta]3AR) and cAMP in maturation- dependent vasorelaxation impairment. Aortic rings from 15 Sprague-Dawley male rats (3 or 9 weeks old) were harvested and left intact or denuded of the endothelium. Vascular relaxation in aortic rings from younger and older groups was compared in the presence of [beta]AR subtype agonists and antagonists along with cAMP and cGMP antagonists. Isolated aortic rings were used to evaluate relaxation responses, protein expression was evaluated by western blot or real time PCR, and metabolites were measured by ELISA. Expression of [beta]AR subtypes and adenylyl cyclase was assessed, and cAMP activity was measured in vascular tissue from both groups. Isoproterenol- and BRL744- dependent relaxation in aortic rings with and without endothelium from 9-week-old rats was impaired compared with younger rats. The [beta]1AR antagonist CG[beta]20712A ([10.sup.-7] M) did not affect isoproterenol or BRL744-dependent relaxation in arteries from either group. The [beta]2AR antagonist ICI-118,551 ([10.sup.-7] M) inhibited isoproterenol-dependent aortic relaxation in both groups. The [beta]3AR antagonist SR59230A ([10.sup.-7] M) inhibited isoproterenol- and BRL744-dependent aortic ring relaxation in younger but not in older rats. All [beta]AR subtypes were expressed in both groups, although [beta]3AR expression was lower in the older group. Adenylyl cyclase (SQ 22536) or protein kinase A (H89) inhibitors prevented isoproterenol-induced relaxation in younger but not in older rats. Production of cAMP was reduced in the older group. Adenylyl cyclase III and RyR3 protein expression was higher in the younger group. In conclusion, altered expression of [beta]3AR and adenylyl cyclase III may be responsible for reduced cAMP production in the older group. Key words: [beta] adrenergic receptors; Vascular tissue; Adenyl cyclase