Nitric oxide-mediated corpus cavernosal smooth muscle relaxation is impaired in ageing and diabetes

Objective To examine nitric-oxide (NO)-mediated relaxation in cavernosal sm ooth muscle in a rat model of diabetes, as previous experiments showed that HbA(1c) (an isoform of glycosylated haemoglobin and a marker of long-term diabetic control) impaired NO-mediated relaxation of normal corpus cavernos al tissue through the generation of superoxide anions. Materials and methods Eight weeks after the induction of diabetes, male Wis tar rats were killed and cavernosal tissue obtained. Strips were contracted with 1 mu mol/L noradrenaline before applying acetylcholine or electrical field stimulation (EFS) or sodium nitroprusside (SNP). Relaxation responses were repeated in the presence of L-arginine (100 mu mol/L), indomethacin ( 10 mu mol/L) or superoxide dismutase (SOD, 120 IU/ mt). Young and age-match ed control animals were examined in the same way. Results Eight weeks of uncontrolled diabetes caused a significant impairmen t in mean relaxation responses to acetylcholine (P<0.05) and to EFS (P<0.05 ), but not to SNP, compared with young and age-matched controls, respective ly. L-arginine, indomethacin and SOD had no significant effect on this impa irment. Ageing caused a lesser but significant impairment in EFS-mediated c avernosal smooth muscle relaxation (P<0.05). Conclusion Diabetes impairs endothelial and neuronal NO-mediated cavernosal smooth muscle relaxation in rats in vitro. This effect is not mediated by an alteration in the intracellular action of NO, the availability of NO, su peroxide anion inactivation of NO or the generation of constrictor prostano ids. It is possible that cholesterol or advanced glycation end products are responsible for the effect of diabetes on penile smooth function.