Abstract
β-adrenoceptor mediated vasorelaxation and cAMP production decline during maturation and aging in rat aorta. β-adrenoceptor-stimulated vasorelaxation is mainly triggered by Gsα-mediated activation of adenylyl cyclase. β2-adrenoceptors can also activate Gi protein which inhibits adenylyl cyclase activity. In this study, we examined the role of Gi proteins in the decreased β-adrenoceptor mediated responses during maturation. Pertussis toxin treatment of aortic rings to inhibit Giα activation completely restored age related decline in isoproterenol-stimulated maximal vasorelaxation in 3-month old rats. This treatment increased the potency, but not the maximal response of isoproteronol to produce vasorelaxation in 6 month old rats. The maximal isoproteronol stimulated cAMP responses were also partially restored in pertussis toxin-treated rings from 3 or 6-month old rats. We also examined β-adrenoceptor stimulated binding of 35[S]GTPγS to Gsα and Giα1/2 in aortic membranes from 1, 3 and 6-month old rats. In 1-month old rats, isoproterenol-stimulated 35[S]GTPγS binding to Gsα was significantly higher than that of 3 or 6-month old rats. Isoproterenol-stimulated 35[S]GTPγS binding to Giα1/2 was found to be significantly increased in 3 or 6-month old rats compared to 1-month old rats. The results of this study showed that β-adrenoceptor-mediated activation of Gs and Gi proteins was declined and increased, respectively, and inhibition of the Gi mediated activity by pertussis toxin treatment partially restored impaired vasorelaxation and cAMP response to β-adrenoceptor stimulation during maturation in rat aorta. The decrease in β-adrenoceptor mediated activation of Gs gradually increased during maturation. All together these results indicated that β-adrenoceptor mainly activates Gs protein in aorta from 1-month old rats, while it activates Gi and with a certain degree of decline it also activates Gs in aorta from 3 and 6-months old rats and not only the increase in β-adrenoceptor coupling to Gi but also the decrease in its coupling to Gs play a role in the impaired β-adrenoceptor responses in rat aorta during maturation.
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