title: Relaxation of rabbit lower urinary tract smooth muscle by nitric oxide and carbon monoxide: modulation by hydrogen peroxide.
abstract: Recent studies suggest that the body produces two gaseous messengers, nitric oxide (NO) and carbon monoxide (CO), both of which activate soluble guanylyl cyclase and thus modulate the activity of smooth muscle cells. In the present study, the effects of NO and CO on the smooth muscle of the lower urinary tract were compared. In addition, the modulation of tissue NO- and CO-induced relaxation by hydrogen peroxide was examined. NO, produced endogenously by electrical field stimulation (EFS) or applied exogenously as a solution, induced a concentration-dependent relaxation of rabbit cavernosal and 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 than the urethra. CO also induced relaxation of both tissue types, but with no apparent difference in sensitivity between the tissues. However, CO was much less potent than NO with respect to smooth muscle relaxation. The mechanism of action of the two mediators was cyclic guanosine monophosphate (cGMP)-dependent, as evidenced by enhanced formation of cGMP and inhibition of relaxation by the guanylyl cyclase inhibitor, oxadiazoloquinoxaline-1-one (ODQ.) 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 both 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, since potentiation by the peroxide was blocked by a specific guanylyl cyclase inhibitor. We suggest that H(2)O(2) may play a positive role in the amplification or NO and CO-mediated responses.
authors.affiliation: Department of Biomedical Sciences, University of Bradford, West Yorkshire, BD7 1DP, UK.
authors.forename: K M
authors.initials: KM
authors.lastname: Naseem
authors.forename: F H
authors.initials: FH
authors.lastname: Mumtaz
authors.forename: C S
authors.initials: CS
authors.lastname: Thompson
authors.forename: M E
authors.initials: ME
authors.lastname: Sullivan
authors.forename: M A
authors.initials: MA
authors.lastname: Khan
authors.forename: R J
authors.initials: RJ
authors.lastname: Morgan
authors.forename: D P
authors.initials: DP
authors.lastname: Mikhailidis
authors.forename: K R
authors.initials: KR
authors.lastname: Bruckdorfer
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology*; D006152:Cyclic GMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology*; D011817:Rabbits; D014521:Urethra / Q000187:drug effects* / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D002248:Carbon Monoxide; D006861:Hydrogen Peroxide; D006152:Cyclic GMP