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 rat bladder tissue. Materials and Methods: Thoracic aortae and urinary bladders were obtained from 55 female Sprague-Dawley rats. The bladder body was used in its original 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, norepinephrine-contracted, rat aortic preparations mounted within urothelium-intact urinary bladder, carbachol caused a concentration-dependent relaxation, amounting 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 resistant to inhibition of the L-arginine/ nitric oxide and cyclo-oxygenase pathways, and unaffected by beta-adrenoceptor blockade and K+ channel inhibition. The relaxation was not associated with any significant changes in the intracellular levels of cGMP or cAMP. Conclusion: A previously unrecognized non-adrenergic, non-nitrergic, non-prostanoid inhibitory mediator is released from the rat urinary bladder by muscarinic receptor stimulation. The physiological importance of such a factor remains to be established.