The interaction of homocysteine and copper markedly inhibits the relaxation of rabbit corpus cavernosum: new risk factors for angiopathic erectile dysfunction?

Objectives To explore whether homocysteine (HCy), an independent risk facto r for atherosclerosis (the angiopathic effect of which occurs through the g eneration of superoxide anions and hydrogen peroxide, augmented by copper, the superoxide anions reacting with nitric oxide, NO, to produce peroxynitr ite. a highly angiopathic free radical) and copper contribute to erectile d ysfunction (EDI through similar mechanisms, by assessing their interactive effects on the relaxation of corpus cavernosum using organ-bath techniques. Materials and methods Cavernosal smooth muscle strips were obtained from ad ult New Zealand White rabbits and mounted in organ baths. After precontract ion with phenylephrine (100 mu mol/L), relaxation responses to carbachol or sodium nitroprusside (SNP) were assessed in the presence or absence of HCy and topper. The effects of HCy and copper in the presence of superoxide di smutase or catalase were also investigated. Results HCy alone inhibited carbachol-stimulated (NO-dependent! but not SNP -stimulated relaxations (NO-independent). This effect of HCy was significan tly augmented by copper, which alone had no effect. The combined effect of HCy and copper was significantly (P<0.05) reversed by superoxide dismutase or catalase, Conclusions HCy inhibited NO-mediated cavernosal smooth muscle relaxation, an effect that was potentiated by copper and reversed by superoxide dismuta se or catalase. It is therefore proposed that the effect of HCB on cavernos al smooth muscle relaxation is mediated by an interaction between NO and su peroxide anions. Moreover, HCy may constitute a new risk factor for angiopa thic ED.