Inhibition of Contractility of Isolated Caprine Detrusor by the Calcium Channel Blocker Cilnidipine and Reversal by Calcium Channel Openers

BACKGROUND: Cilnidipine is a fourth-generation calcium channel blocker that is clinically used to treat hypertension. It is a dihydropyridine that blocks L- and N-type calcium channels. The inhibitory effect of cilnidipine on isolated detrusor muscle contractility has not been studied. This study investigated the inhibitory effect of cilnidipine on isolated caprine (goat) detrusor muscle contractility and the reversal of the inhibition by calcium channel openers. METHODS: Fourteen caprine detrusor strips were made to contract using 80 mM potassium chloride before and after addition of three concentrations (20, 40, and 60 µM) of cilnidipine. Two reversal agents, the L-type calcium channel opener FPL64716, and the N-type calcium channel opener GV-58, were investigated for their ability to reverse the inhibitory effect of 40 µΜ cilnidipine on potassium chloride-induced detrusor contractility. RESULTS: Cilnidipine caused a dose-dependent and statistically significant inhibition of detrusor contractility at all concentrations of cilnidipine used (20, 40, and 60 µΜ). The inhibitory effect of 40 µM cilnidipine on detrusor contractility was significantly reversed by the addition of FPL64716 and GV-58. CONCLUSIONS: Cilnidipine inhibits the contractility of the isolated detrusor by blocking L- and N-type calcium channels. Cilnidipine could be evaluated for treating clinical conditions requiring relaxation of the detrusor such as overactive bladder.