Penile Expression of Hypoxia-inducible Factor-1alpha, Vascular Endothelial Growth Factor, and Nitric Oxide Synthase in the Type II Diabetic Rat / 대한남성과학회지

ABSTRACT

PURPOSE: Erectile dysfunction(ED) is commonly experienced in men with diabetes mellitus. Hypoxia in the penile tissue by vascular complications is regarded as a pathophysiologic factor in diabetic ED. The aim of this study is to investigate whether HIF-1alpha is altered in diabetic penile tissues and whether its alteration may modulate penile expression of VEGF and NOS, which are believed to play a role in diabeteic ED. MATERIALS AND METHODS: OLETF rats, an animal model for type II diabetes mellitus, and LETO rats, a non-diabetic control group, were used. We analyzed the distribution of HIF-1alpha, VEGF, and NOS(eNOS and iNOS) in the isolated corupus cavernosum of both LETO and OLETF rats by immunohistochemicalstaining. The mRNA expression levels of HIF-1alpha, VEGF, eNOS, and iNOS were also analyzed by reverse transcriptase-polymerase chain reaction(RT-PCR). RESULTS: There was no difference in the concentration of nitrite/nitrate in cavernosal homogenate between LETO rats and OLETF rats. By immunohistochemical staining. HIF-1alpha, VEGF, and iNOS were expressed more abundantly in stain in OLETF rats. By RT-PCR analysis, HIF-1alpha mRNA, VEGF mRNA and iNOS mRNA expression levels were higher in the OLETF rats compared to LETO rats. CONCLUSIONS: We suggest that increased HIF-1alpha, VEGF and iNOS expressions in OLETF rat may be associated with microvascular injury in corpus cavernosum. Such microvascular injury is proposed to be associated with vasculogenic erectile dysfunction.