Relaxant effects of β‐adrenergic agonists on porcine and human detrusor muscle

Abstract

Relaxant effects of different beta-adrenoceptor agonists on porcine and human detrusor were examined. Thus, the beta-adrenoceptor subtype mainly responsible for relaxation in the detrusor muscle of pigs was characterized. Additionally, different effects of several beta-agonists in both species were shown. Experiments were performed on muscle strips of porcine and human detrusor suspended in a tissue bath. The relaxant effects of the non-selective beta-agonist isoprenaline, the selective beta2-agonists procaterol, salbutamol and the selective beta3-agonists BRL 37344, CL 316 243 and CGP 12177 on potassium-induced contraction were investigated. The inhibitory effect of different substances on the maximum contraction and the rank order of potency for endogenous catecholamines was determined in pigs. Furthermore, concentration-relaxation curves were performed for pigs and humans. Pigs: In the pre-treatment experiments isoprenaline and procaterol showed similar effects. The concentration-response experiments showed that the maximum relaxation induced by procaterol and salbutamol was more than 90%, not significantly different from isoprenaline, whereas the maximum relaxations of CL 316 243, BRL 37344 and CGP 12177 amounted to 68, 70 or 30%, respectively. Rank order of potencies was isoprenaline > or = adrenaline > noradrenaline. Humans: Isoprenaline, procaterol, salbutamol and CL 316 243 showed a maximum relaxation of 80, 41, 24 and 35% and pD2 values of 6.24, 5.65, 5.48 and 5.55, respectively. Beta2-receptors play a main functional role in mediating relaxation of porcine detrusor. Selective beta2- and beta3-agonists similarly relax the human detrusor. Effects were smaller compared with the pig.