Characterization of the urinary bladder dysfunction in renovascular hypertensive rats

Abstract

Association between arterial hypertension and urinary bladder dysfunction has been reported in humans and spontaneously hypertensive rats. However, no study exists evaluating the bladder dysfunction in conditions of renovascular hypertension. The purpose of this study was to characterize the bladder dysfunction in two kidney-one clip (2K-1C) hypertensive rats. Methods: A silver clip was placed around the renal artery of male Wistar rats. After 8 weeks, cystometric study, concentration-response curves to contractile and relaxant agents, frequency-dependent contractions, histomorphometry, muscarinic M(2)/M(3) mRNA expression and cyclic AMP measurements were performed. Results: 2K-1C rats showed enhanced bladder volume, wall thickness and smooth muscle density. 2K-1C rats also exhibited increases in bladder capacity and non-void contractions, and decreases in the inter-contraction intervals. In isolated detrusor smooth muscle (DSM), contractions to carbachol and electrical-field stimulation (EFS) were significantly greater in 2K-1C rats. The Rho-kinase inhibitor Y27632 (10 mu M) significantly reduced the carbachol-induced contractions in SHAM and 2K-1C rats, but DSM remained overactive in 2K-1C rats in presence of Y27632. Concentration-dependent contractions to the P2X receptor agonist alpha,beta-methylene ATP, KCl and extracellular Ca(2+) did not change between SHAM and 2K-1C groups. In 2K-1C rats, isoproterenol, metaproterenol and BRL 37-344 (non-selective, beta(2)- and beta(3)-selective adrenoceptor agonists, respectively) produced significantly lower relaxations and decreased cAMP levels, whereas relaxant responses to sodium nitroprusside and BAY 41-2272 remained unchanged. Muscarinic M(3) mRNA expression receptors were higher in 2K-1C group. Conclusions: Renovascular hypertensive rats exhibit bladder dysfunction that involves tissue remodeling and enhanced muscarinic M(3)-mediated contractions associated with reduced beta-adrenoceptor-mediated signal transduction