Pharmacological Characterization of the Isolated Canine Prostate

Abstract

Purpose The goal of the present study was to characterize the responses of the isolated normal canine prostate to various contracting and relaxing stimuli to determine which pharmacological agents may have utility against the dynamic component of benign prostatic hyperplasia (BPH). Materials and Methods Isometric force development was measured in isolated strips of prostate tissue. Results The alpha-adrenergic agonists were the most efficacious stimulants tested (phenylephrine EC 50 = 2.1 micromolar). Endothelin-1, acting primarily via ET A receptors, was more potent (EC 50 = 27 nM.) but less efficacious. Histamine (EC 50 = 14.7 micromolar), serotonin (EC sub 50 = 0.12 micromolar), carbachol (EC 50 = 5.9 micromolar) and KCl (EC sub 50 = 48.8 mM.) were also less efficacious than phenylephrine. Nifedipine was a potent (IC 50 = 28 nM.) and efficacious (74 percent inhibition) inhibitor of phenylephrine-induced force. Potassium channel activator drugs were also efficacious relaxants, producing approximately 80 percent inhibition of force; rank order of potency was P1075 greater than cromakalim greater than diazoxide. Sodium nitroprusside was a weak relaxant, producing only approximately 40 percent relaxation at a concentration of 100 micromolar. Both isoproterenol and forskolin were effective relaxants (75 to 90 percent relaxation). Conclusions We conclude that potassium channel activators, adenylate cyclase stimulators, or endothelin antagonists may have utility against the dynamic component of outflow obstruction secondary to BPH.