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, intravenously) was given to rabbits for 14 days. Rabbit bladder and urethral smooth muscles were then isolated and evaluated using a muscle bath technique.


RESULTS
10(-10)-5 x 10(-6)M CsA alone had no direct effect on bladder or urethral smooth muscles. The Emax (maximum contractile response) and ED50 values for acetylcholine-induced contractions and the Emax (maximum relaxation response) for isoproterenol-induced relaxation in bladder smooth muscles were not significantly different between CsA-treated and control groups. The ED50 for isoproterenol-induced relaxation was significantly lower in the CsA group (P < 0.05). The Emax for phenylephrine- and clonidine-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 phenylephrine and clonidine in Ca+2-free solution to the normal solution in the CsA group (13.42% and 4.40%, respectively) was significantly higher than the maximal response ratios in the control group (6.34% and 3.00%, respectively; P < 0.05).


CONCLUSIONS
CsA treatment augments the relaxation response of the bladder to isoproterenol and the contractile response of the urethra to phenylephrine and clonidine. In addition, CsA increases the filling of intracellular stores of releasable Ca+2, and also increases the permeability of Ca+2 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.
Kitani
K
K
Department of Urology, Kumamoto University School of Medicine, Japan.
Machida
J
J
Wada
Y
Y
Yoshida
M
M
Ueda
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D014521:Urethra / Q000187:drug effects* / Q000502:physiology; D001743:Urinary Bladder / Q000187:drug effects* / Q000502:physiology
D010656:Phenylephrine; D016572:Cyclosporine; D007545:Isoproterenol; D003000:Clonidine; D000109:Acetylcholine