Initial validation of a novel rat model of vasculogenic erectile dysfunction with generalized atherosclerosis

Abstract

Although rats have been widely used in evaluating various causes of vasculogenic erectile dysfunction (VED), the atherosclerotic rat model has seldom been tried probably due to its inherent tolerance to a cholesterol diet. To enhance endothelial sensitivity to cholesterol diet, we tested the effects of transient interruption of nitric oxide synthase on atherogenesis induced by cholesterol diet in a rat model. Rats with atherosclerosis (AS group) received 1% cholesterol diet for 6 weeks. During the initial 2 weeks, they drank water that contained N(G)-nitro-L-arginine methyl ester (L-NAME) (3 mg/ml). After 6 weeks, we carried out histologic and hemodynamic evaluation to confirm pelvic atherosclerosis and erectile dysfunction, respectively, and the results were compared with those of cholesterol only (Chol) group and normal control (C) group. Compared to the C or Chol group, the mean intima/media (I/M) of the internal pudendal artery, which contributes approximately 70% of the total resistance of the penile vasculature, was markedly increased by the treatment (1.82+/-0.25 vs 0.77+/-0.13, P<0.05). Correspondingly, significantly diminished erectile function was observed. Combined treatment for 2 weeks elicited early atherosclerotic changes in proximal arteries and erectile impairment and further 4 weeks of cholesterol diet spread overt atherosclerosis to the periphery. The Chol group showed no arterial pathology, although they showed mild VED. A correlation study showed that atherosclerosis of the distal artery was better correlated with erectile dysfunction than the proximal artery. Based on these results, our study demonstrates that combination treatment of cholesterol diet with L-NAME would be used as a rapid, effective protocol of developing atherosclerotic rat model of VED.