Altered ureteral contractility with ageing: Role of the rho-kinase pathway

This study investigated the role of calcium sensitisation in the regulation of ureteral contractility with ageing. Isolated ureteral strips from young (6-month old) and older (3-year old) pigs were mounted in Krebs bicarbonate solution and contractility induced by the α1-adrenoceptor agonist phenylephrine (30 and 300 μM) and 5-HT (10 and 100 μM), recorded in the absence and presence of the rho-kinase inhibitors Y-27632 (10 μM) and fasudil (30 μM). Ureteral strips developed bursts of contractile activity which was measured as area under the curve (AUC) and frequency. Maximum contraction to phenylephrine was significantly enhanced in tissues from older animals compared to younger animals (p < 0.001) while maximum contraction to 5-HT was greater in tissues from younger animals (p < 0.001). Both inhibitors significantly depressed AUC and frequency responses to both agonists in ureters from both age groups (p < 0.05). Inhibition by Y-27632 of phenylephrine (300 μM)- and 5-HT(100 μM)-induced contractions was greater in tissues from older animals than young (p < 0.05). Rho-kinase activity was also assayed in ureteral tissues, and basal activity was similar in ureters from both age groups. Neither phenylephrine nor 5-HT increased rho-kinase activity over basal levels. These data demonstrate the significant role rho-kinase plays in ureteral contractility and possible alterations with age.