Calcification of the cavernosal bodies may be responsible for development of erectile dysfunction in uremic apolipoprotein E deficient (apoE-/-) mice.

Abstract

INTRODUCTION AND OBJECTIVE\nErectile dysfunction s physiopathology in uremia is complex and multifactorial, involving a combination of classical risk factors and specific uremia-related risk factors such as increased oxidative stress, endothelial dysfunction and inflammation. The aim of the study is to investigate the effect of chronic kidney disease (CKD) on vascular calcification and endothelial function of cavernosal bodies in apolipoprotein E deficient (apoE-/-) mice, a well known model of erectile dysfunction.\n\n\nMATERIALS AND METHODS\nEight-week-old male apoE-/- mice were randomly assigned to the following 3 groups: (i) subtotally nephrectomised (SNX apoE-/-, 12 mice), (ii) uninephrectomised (UNX apoE-/-, 11 mice) or (iii) sham operated (sham-op apoE-/-, 15 mice). At 16 weeks after surgery, aortas and penile erectile tissues were harvested for histological studies to assess atherosclerosis, vascular calcification, nitrotyrosine staining, total collagen content and macrophage staining.\n\n\nRESULTS\nAt sacrifice, SNX and UNX mice had significantly higher serum urea, total cholesterol, and triglyceride concentrations than sham-op controls. Atherosclerotic lesions in thoracic aorta were significantly larger in uremic apoE-/- mice than in controls. There were no atheromatous lesions in cavernosal bodies or penile artery observed in any group. However, SNX and UNX animals showed a significant increase in calcification score, collagen content and nitrotyrosine staining in cavernosal bodies when compared with controls. The degree of macrophage infiltration was comparable between the 3 groups.\n\n\nCONCLUSION\nIn conclusion, even mild renal dysfunction, i.e., after uninephrectomy increases calcification score and aggravates endothelial function of cavernosal bodies in apoE-/- mice and this effect might be linked to increased oxidative stress in penile endothelium.