A non-nitrergic smooth muscle relaxant factor released from rat urinary bladder by muscarinic receptor stimulation

Purpose: To study the possible release of a relaxant factor from isolated r at bladder tissue. Materials and Methods: Thoracic aortae and urinary bladders were obtained f rom 55 female Sprague-Dawley rats. The bladder body was used in its origina l tubular shape as the donor tissue in a co-axial bioassay system, and the aorta served as acceptor tissue. Results: In a co-axial bioassay system with endothelium-free, norepinephrin e-contracted, rat aortic preparations mounted within urothelium-intact urin ary bladder, carbachol caused a concentration-dependent relaxation, amounti ng to 64 +/- 7% (n = 10) of the induced contraction, suggesting release of a relaxing factor. The relaxant effect of carbachol was lost if the urinary bladder segment was removed. However, the relaxation was affected neither by removal of the urothelium, nor by bladder segment inversion. It was resi stant to inhibition of the L-arginine/ nitric oxide and cyclo-oxygenase pat hways, and unaffected by beta-adrenoceptor blockade and K+ channel inhibiti on. The relaxation was not associated with any significant changes in the i ntracellular levels of cGMP or cAMP. Conclusion: A previously unrecognized non-adrenergic, non-nitrergic, non-pr ostanoid inhibitory mediator is released from the rat urinary bladder by mu scarinic receptor stimulation. The physiological importance of such a facto r remains to be established.