Direct Effect of Carbon Monoxide on Relaxation Induced by Electrical Field Stimulation in Rat Corpus Cavernosum

PURPOSE: Carbon monoxide (CO) may mediate smooth muscle relaxation in the rat corpus cavernosum smooth muscle (CCSM). We hypothesized that CO plays a role in neurally derived, frequency-dependent relaxation of rat CCSM. MATERIALS AND METHODS: To study the effect of CO on CCSM relaxation induced by electrical field stimulation (EFS), a CCSM bundle was mounted on a force transducer and perfused with Hanks' balanced salt solution at 37℃ with 95% O(2) and 5% CO(2). After 1 hour equilibration with -500 mg of passive tension, contraction of the CCSM bundle was elicited by 10(-5) M phenylephrine, which was continuously added with different concentrations of CO (1%, 2%, and 5%). Frequency-dependent relaxation was induced by EFS trains (0.2 ms at 0.5-32 Hz, for 10 s) repeated at 2 min intervals over 15 min in the presence of adrenergic and muscarinic receptor blocking agents (guanethidine and atropine, respectively). To study the distribution of heme oxygenase-2 (HO-2) in the rat CCSM, we performed immunohistochemical evaluation. RESULTS: CO produced a dose-dependent enhancement of EFS-induced relaxation. Pretreatment with N(G)-nitro-L-arginine (a nitric oxide synthase blocker) greatly reduced the EFS-induced relaxation in the presence of CO (-45%). Pretreatment with zinc protoporphyrin-IX (ZnPP-9, a heme oxygenase inhibitor) had no significant effect on EFS-induced relaxation in the absence or the presence of CO. We found immunoreactivity for HO-2 in CCSM and immunoreactivity for protein gene product 9.5 (PGP 9.5) in nerve fibers. CONCLUSIONS: We conclude that CO produced a dose-dependent enhancement of EFS-induced relaxation in rat CCSM bundles, but neurally derived, frequency-dependent relaxation in the rat CCSM depended mostly on nitric oxide in response to nonadrenergic noncholinergic neurotransmission. Immunoreactivity for HO-2 was found in rat CCSM but not nerve fibers.