A mouse model of hypercholesterolemia-induced erectile dysfunction.

Introduction: Hypercholesterolemia is one of the most important risk factors for the development of erectile dysfunction (ED) in men.

Aim: We employed an established mouse model of hypercholesterolemia.

Main Outcome Measures: We test for abnormalities in vasoreactivity in corporal tissue and temporally correlated changes in vasoreactivity with alterations in histology and protein expression.

Methods: A total of 150 mice were studied. A total of 100 apolipoprotein-E knockout (ApoE(-/-)) mice were fed a 1.25% cholesterol diet for 2, 4, 8, and 12 weeks (N = 25/group), while a group of ApoE(-/-) and wild-type Bl-6 mice were fed a normal diet. The study was terminated, and all mice were harvested at 22 weeks of age for vasoreactivity, histology, and protein studies from corporal tissues. Dose-response curves were generated to evaluate endothelium-dependent and endothelium-independent vasoreactivity, ex vivo. The contents of endothelial cells, smooth muscle cells, and smooth muscle/collagen ratio were assessed by immunohistochemistry staining or Masson staining. Level of cyclic guanosine monophosphate (cGMP) was detected by enzyme immunoassay assay. Levels of phosphorylated endothelial nitric oxide synthase (p-eNOS)/total eNOS, neuronal nitric oxide synthase (nNOS), and cyclic GMP-dependent kinase (cGK-1) protein were assessed by Western analysis.

Results: Abnormalities in endothelium-dependent and endothelium-independent vasoreactivities, endothelial content, smooth muscle/collagen ratio, p-eNOS phosphorylation at Ser1177 only, nNOS, cGMP, and cGK-1 changed with the different durations of the high-cholesterol diet.

Conclusions: These data demonstrate that this mouse model is suitable for investigating aspects of hypercholesterolemic ED.