The Action Mechanism of Relaxation Effect of Atropine on the Isolated Rabbit Corpus Cavernosum

Choi, Young Deuk; Chung, Woo Sik; Ha, Jong Sik; Kwon, Sung Won

Abstract

Atropine is the classic antimuscarinic anticholinergic drug that bas been used to block cholinergic neurotransmission in basic research and received recent interest clinically in the intracavernous pharmacotherapy of erectile dysfunction. It has been suggested that at low dose(0.00000001M), atropine blocks muscarinic receptors, thereby reducing both cholinergic of the adrenergic and cholinergic excitation of the NANC neuroeffector systems, on the other hand, at large pharmacological dose(0.001M),induces the release of EDRF which recently has been identified as nitric oxide(NO) or NO like substance. Therefore, we tried to confirm the action of atropine in the cavernosal tissue and define its mechanism. Strip of rabbit corpus cavernosum were isolated and mounted in 10 ml organ chambers to measure isometric tension. Muscle strips submaximally precontracted with phenylephrine(5x0.000001M) and treated with increasing concentrations of atropine(0.00000000001M to 0.00lM) showed tension increase upto 0.00000001M of atropine, and thereafter, relaxed concentration dependently(0.0000001M: 43.7%, 0. 000001M: 63.0%,0.00001M:86.2%,0.0001M:93.6%,0.001M:100%). Relaxations to atropine(5x0.000001M) were not inhibited even partially by endothelial disruption or by pretreatment with methylene blue or pyrogallol. Pretreatment of muscle strips with atropine(5x0.00000lM) caused concentration- related inhibition of a phenylephrine induced contraction, and in calcium-free high potassium depolarizing solution, decreased basal tension as well as inhibited contraction induced by CaC12. However, atropine did not produce reduction of responses to depolarizing medium(20, 40, 80mM KCl). With these results we can confirm the relaxation effect of atropine at a larger dose(>0.0000001M)on the cavernosal smooth muscle and suggest that its action is mediated by increasing intracellular calcium sequestration,not by hyperpolarization or EDRF.