Atropine is the classic antimuscarinic anticholinergic drug that has 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 (10E-8M), 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 pharmacologic dose (10E-3M0,
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.
Strips of rabbit corpus cavernosum were isolated and mounted in 10 ml organ chambers to measure isometric tension. Muscle strips submaximally precontracted with phenylephrine (5×10E-6M) and treated with increasing concentrations of atropine
(10E-11M to
10-3M) showed tension increase upto 10E-8M of atropine, and thereafter, relaxed concentration-dependently (10E-7M: 43.7%, 10E-6M: 63.0%, 10E-5M: 86.2%. 10E-4M: 93.6%, 10E-3M: 100%). Relaxations to atropine (5×10E-6M) were not inhibited even
partially
by endothelial disfuption or by pretreatment with methylene blue or pyrogallol. Pretreatment of muscle strips with atropine (5×10E-6M) caused concentrration-related inhibition of a phenylephrine induced contraction., and in calcium-free high
potassium
depolarizing solution, decreoased basal tension as well as inhibited contraction induced by CaCl2. However, atropine did not produce reduction of responses to depolarizing medium (20, 40, 80mM KCI).
With these results we can confirm the relaxation effect of atropine at a larger dose (>10E-7M) on the cavern
osal smooth muscle and suggest that its action is mediated by increasing intracellular calcium sequestration, not by hype4rpolarization or EDRF.
|