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 inve stigation was to determine if cholera toxin-mediated vasorelaxation was als o 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 pheny lephrine was assessed along with relaxation to cholera toxin (azide-free), isoproterenol, and forskolin. There were no age-related changes to KC? or p henylephrine contraction. There xas a significant decrease with age in rela xation 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 si gnificant decrease with age in the maximal relaxation to cholera toxin as w ell as a rightward shift in the dose-response curve. Cholera toxin-stimulat ed adenosine 3',5'-cyclic phospate (cAMP) levels were measured and there Ha s no increase in cAMP levels surrounding the time period associated with re laxation induced by cholera toxin. These data suggest that different precon stricting agents markedly affect the age-related changes in beta-adrenergic -mediated vasorelaxation. Furthermore, they suggest that the mechanism of c holera toxin-mediated vasorelaxation may not be mediated through increases in cAMP concentration.