Impaired Cholera Toxin Relaxation With Age in Rat Aorta

J. Chapman, W. E. Schutzer, V. J. Watts, S. L. Mader
1999 The journals of gerontology. Series A, Biological sciences and medical sciences  
Beta-adrenergic-mediated vasorelaxation declines withmaturation and aging. Availoble datasuggestthatimpaired stimula-toryG-protein junction could explain thisdeficit. Wehavepreviously found a lossof cholera toxin (CT)-stimulated adenosinediphosphate (ADP) ribosylation withage in rat aortic membranepreparations, withoutevidence for lossofthe stimulatory alpha subunit of G protein (Gsa) by immunoblotting. The purpose of this investigation was to determine if cholera toxin-mediated vasorelaxauon
more » ... ted vasorelaxauon wasalso impaired withage.Aortic ring segments from 6 weeks, 6 months, 12 months, and 24 months old male F-344 rats were used. Contraction to KCIand phenylephrine was assessed along withrelaxation to cholera toxin (azide-free), isoproterenol; and forskolin. There were no age-reWed changes to KQ or phenylephrine contraction. There was a significantdecrease with age in relaxation to isoproterenol. This loss with age was significantly greater withKCl-preconstricted vessels thanphenylephrine-preconstricted vessels. Therewereno age-reWed changes in the relaxation toforskolin. There wasa significant decrease with age in the maximalrelaxauon to cholera toxin as wen as a rightward shift in the dose-response curve. Cholera toxin-stimulated adenosine 3', 5'-cyclic phospate(cAMP) levels were measured and there was no increase in cAMP levels surrounding the timeperiodassociated with relaxation inducedby cholera toxin. These data suggestthat differentpreconstricting agents markedly affect the age-related changes in betaadrenergic-mediated vasorelaxation. Furthermore, they suggestthat the mechanism ofcholera toxin-mediated vasorelaxationmaynotbe mediated throughincreases in cAMPconcentration.
doi:10.1093/gerona/54.4.b154 pmid:10219003 fatcat:5y4t6zk7wzaxjhum3b5xrdipqu