Impaired cholera toxin relaxation with age in rat aorta

Beta-adrenergic-mediated vasorelaxation declines with maturation and aging. Available data suggest that impaired stimulatory G-protein function could explain this deficit. We have previously found a lass of cholera toxin (CT)-stimulated adenosine diphosphate (ADP) ribosylation with age in rat aortic membrane preparations, without evidence for loss of the stimulatory alpha subunit of G protein (Gs alpha) by immunoblotting. The purpose of this investigation was to determine if cholera toxin-mediated vasorelaxation was also impaired with age. Aortic ring segments from 6 weeks, 6 months, 12 months, and 24 months old male F-344 rats were used. Contraction to KCl and phenylephrine was assessed along with relaxation to cholera toxin (azide-free), isoproterenol, and forskolin. There were no age-related changes to KC? or phenylephrine contraction. There xas a significant decrease with age in relaxation to isoproterenol. This loss with age was significantly greater with KCl-preconstricted vessels than phenylephrine-preconstricted vessels. There were no age-related changes in the relaxation to forskolin. There was a significant decrease with age in the maximal relaxation to cholera toxin as well as a rightward shift in the dose-response curve. Cholera toxin-stimulated adenosine 3',5'-cyclic phospate (cAMP) levels were measured and there Has no increase in cAMP levels surrounding the time period associated with relaxation induced by cholera toxin. These data suggest that different preconstricting agents markedly affect the age-related changes in beta-adrenergic-mediated vasorelaxation. Furthermore, they suggest that the mechanism of cholera toxin-mediated vasorelaxation may not be mediated through increases in cAMP concentration.