Relaxation of rabbit lower urinary tract smooth muscle by nitric oxide andcarbon monoxide: modulation by hydrogen peroxide

Recent studies suggest that the body produces two gaseous messengers, nitri c oxide (NO) and carbon monoxide (CO), both of which activate soluble guany lyl cyclase and thus modulate the activity of smooth muscle cells. In the p resent study, the effects of NO and CO on the smooth muscle of the lower ur inary tract were compared. In addition, the modulation of tissue NO- and CO -induced relaxation by hydrogen peroxide was examined. NO, produced endogen ously by electrical field stimulation (EFS) or applied exogenously as a sol ution, induced a concentration-dependent relaxation of rabbit cavernosal an d urethral smooth muscle strips, but not of bladder tissues. The cavernosal tissue was found to be three times more sensitive to the actions of NO tha n the urethra. CO also induced relaxation of both tissue types, but with no apparent difference in sensitivity between the tissues. However, CO was mu ch less potent than NO with respect to smooth muscle relaxation. The mechan ism of action of the two mediators was cyclic guanosine monophosphate (cGMP )-dependent, as evidenced by enhanced formation of cGMP and inhibition of r elaxation by the guanylyl cyclase inhibitor, oxadiazoloquinoxaline-1-one (O DQ.) The data suggests that NO is the dominant messenger in these tissues, but does not exclude a role for CO. In the presence of hydrogen peroxide, the relaxation responses induced by b oth NO and CO were significantly increased, regardless of tissue type. The mechanism for this effect is unclear, but evidence points to a requirement for the activation of guanylyl cyclase and enhanced formation of cGMP, sinc e potentiation by the peroxide was blocked by a specific guanylyl cyclase i nhibitor. We suggest that H2O2 may play a positive role in the amplificatio n or NO and CO-mediated responses. (C) 2000 Elsevier Science B.V. All right s reserved.