Effects of diabetes on nitric oxide-mediated relaxations in male rat corpus cavernosum smooth muscle

INTRODUCTION: We evaluated the effects of diabetes on nitric oxide-mediated relaxations and nitric oxide synthase activity in male rat corpus cavernosum smooth muscles. METHODS: Eight-week-old male rats were assigned to three groups: control (injected with the vehicle), DM (diabetes mellitus, induced by injection with 65 mg/kg streptozotocin), and TES (testosterone, testosterone supplemented after induction of diabetes). After 8 weeks, corpus cavernosum smooth muscle strips were mounted in an organ bath for isometric tension recordings. Electrical field stimulation (EFS, 2-ms pulse duration, 0.3-20 Hz and 3 s train) was applied to the strips precontracted with 30 microM phenylephrine. The microdialysis probe was inserted into the strip, and Krebs-Henseleit solution was perfused into the probe. The dialysate during EFS was collected, and the amount of NO(-)(2)/NO(-)(3) (NOx) released in the dialysate was measured by the Greiss method. Sodium nitroprusside (0.1 nM to 10 mM) and carbachol (1 nM to 10 mM) were cumulatively added to the strips precontracted with 30 microM phenylephrine. RESULTS: EFS caused frequency-dependent relaxations and NOx releases of the strips. Pretreatment with N(omega)-nitro-L-arginine (100 microM) and tetrodotoxin (1 microM) completely inhibited the relaxations and NOx releases. The maximum relaxation was significantly greater in the DM group than in the control or TES group. The release of NOx was significantly greater in the DM group than in the control or TES group. Sodium nitroprusside, the endothelium-independent vasodilator, relaxed the tissues in all three groups. There were no significant differences among control, DM and TES groups in the maximum relaxation to sodium nitroprusside. CONCLUSION: The present data suggest that diabetes enhances nitric oxide synthase activity and nitric oxide-mediated relaxations in the male rat corpus cavernosum by the reduced testosterone level in the diabetic animals.