Effect of cyclosporin A on isolated rabbit bladder and urethral smooth muscle.

Background: The effects of Cyclosporin A (CsA) on vascular smooth muscle inducing hypertension have been established. However, there is no information available concerning the effects of CsA on urinary smooth muscle. Therefore, the effects of CsA were investigated on the bladder and urethral smooth muscle in rabbits. Methods: CsA (10 mg/kg/day. intravtmouslyl was given to rsbbits for 14 days. Rabbit bladder and urethral smooth muscles were then isolated and evaluatd using a muscle bath technique. Results: 10 111-- 5 × 10 M CsA done had no direct effect on bladder or urethral smooth muscles. The Emax. (maximum contractile response) and ED values for acetylcholine-induced contraclions and the Emax (maximum relaxation response) for isoproterenol-induced relaxation in bladder smooth muscles were not significantly different between CsA-treated and control grouos. The ED for isoproterenol-induccd relaxation was significantly lower in the CsA group (P< 0.05). The Emax for phenylephrine- and clonidinci-induced contractions in urethral smooth muscle was significantly higher in the CsA-treated group (P< 0.05). The ratio of the maximum response of the urethral smooth muscle to phepylephrine. and clonidine in Ca free solution to the normal solution in the CsA group (1 3.42% and 4.40%, respectively was signiticantly higher than the maximal response ratios in the control group th.34%, and 3.00%, respectively; P<0.05. Conclusions: CsA treatmemt augments the relaxation response of the bladder to isoprolerenol and the contractile response of the urethra to phenylephrine and clonidine. In addition, CsA increases the iilling of intracellular stores of releasable Ca++, and also increases the permeability of Ca++ in rabbit urethral smooth muscle. Thus, it is suggested that CsA may cause a urinary disturbance in patients treated with CsA via increased urethral resistance.