β‐Adrenergic receptor (βAR) agonists effectively relax rat bladder detrusor irrespective of contractile stimulus

Abstract

Apart from muscarinic receptors other stimuli can contribute to bladder contraction in pathological settings. Therefore, we have studied whether the type of contractile stimulus affects bladder relaxation by the βAR agonist isoproterenol (ISO) in isolated strips from adult male Wistar rats (J Pharmacol Exp Ther 313: 260-267, 2005). Relaxation was measured against passive tension (10 mN) or active tension induced by the muscarinic agonist carbachol (1 μM), 100 μM serotonin, 3 μM bradykinin or receptor-independently by 50 mM KCl. Relaxation was expressed relative to the effect of the receptor-independent relaxant forskolin (10 μM). Data are means ± SEM (n = 6-8). Prior to adding ISO, active tension was 24 mN (carbachol), 11 mN (serotonin), 14 mN (bradykinin) and 40 mN (KCl). The relaxation by forskolin was 51 ± 3%, 75 ± 3%, 65 ± 2%, 70 ± 2% and 57 ± 1% against passive tone, carbachol, serotonin, bradykinin and KCl, respectively. Relaxation by ISO against carbachol was maximally 57 ± 2% of forskolin effects and occurred with an EC50 of 54 nM. Against all other stimuli ISO was significantly more potent and more effective (EC50: 1.8, 2.9, 2.2 and 10 nM; maximum effect: 84 ± 2%, 91 ± 1%, 79 ± 2% and 80 ± 1% against passive tension, serotonin, bradykinin and KCl, respectively; all p < 0.05 vs. carbachol). We conclude that βAR are effective bladder relaxants against various contractile stimuli, with the muscarinic receptor-mediated contraction being least sensitive. We propose that they may be even more effective under pathophysiological conditions than in normal bladder. Supported by DFG and Boehringer Ingelheim.