Lluel_2003_Fundam.Clin.Pharmacol_17_633

Our objective was to study age-related changes in adrenergic contractility and gene expression profile in the rat urinary bladder. Young (3-month old), adult (10-month old) and senescent (30-month old) male WAG/Rij rats were used. Gene expression profile in the rat urinary bladder was defined using Atlas microarray technology. In vitro contractile responses induced by KCl, phenylephrine (PHE) and norepinephrine (NE) were compared in isolated urinary bladders dissected from young, adult and senescent rats. Among a total of 1176 genes present on the arrays, 15 genes showed an increase in expression and 10 genes a decrease with age. Four genes related to nerve growth factor were upregulated whereas NOS type III was downregulated in aging rats. Intrinsic contractility of isolated rat urinary bladders was not changed between adult and aging rats as judged by the response curves to KCl. In contrast, an age-related increase in the maximal contractile responses to NE, but not PHE, was noticed (13 +/- 1, 48 +/- 2% and 59 +/- 2% at 3, 10 and 30 months, respectively). The alpha1D-adrenoceptor antagonist BMY7378 antagonized NE-induced contractions with low potency in both groups suggesting the involvement of the alpha1A-adrenoceptor subtype. This was confirmed by microarray, which demonstrated mRNA expression for the alpha1A-adrenoceptor subtype only. These results suggest that aging of the urinary bladder is associated with an increase in the maximal contractile response to NE which could be due to NO shortage resulting from downregulation of urothelial NOS III.