Venlafaxine Inhibits Detrusor Contractions in Rats: A Role for Extracellular Calcium

Abstract

Background and Objective: Certain antidepressant drugs cause urinary incontinence while some of that are used to treat incontinence. This study was aimed to investigate the possible effects of venlafaxine in rat bladder detrusor muscle and the mechanisms involved in the inhibitory effect of contraction. Methodology: Strips of rat detrusor muscle were suspended in a perfusion organ bath. The contractile response to electrical field stimulation, acetylcholine and potassium chloride were determined after the addition of venlafaxine. To investigate the association of venlafaxine and other systems, it has been used nonselective beta blocker propranolol, nonselective serotonin receptor blocker methysergide, opioid receptor antagonist naloxone and non-selective alpha adrenergic receptor antagonist phentolamine. To demonstrate the role of calcium on the effect of venlafaxine on isolated detrusor muscle, diltiazem was used as a calcium channel blocker. For statistical analysis one-way analysis of variance (ANOVA) with the Tukey-Kramer post-hoc test was used. Results: Venlafaxine (5x10(-4) M) inhibited the maximum contractile response to electrical field stimulation, acetylcholine and potassium by 73% (p<0.001), 36% (p<0.001), 87% (p<0.001), respectively. Propranolol, phentolamine, methysergide and naloxone did not change the inhibitory effect of venlafaxine on electrical field stimulation response. The maximum contractile response to 10(-3) M acetylcholine was reduced by 76% of control (p<0.001) in the presence of 10(-4) M diltiazem. The administration of venlafaxine (5 x 10(-4) M) in combination with diltiazem (10(-4) M) did not change the contractile responses of acetylcholine compared to diltiazem alone. Conclusion: It is concluded that venlafaxine inhibits rat detrusor muscle contraction via the inhibition of calcium influx from the extracellular space.