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.
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.
Authors: Biljana Musicki; Tongyun Liu; Gwen A Lagoda; Travis D Strong; Sena F Sezen; Justin M Johnson; Arthur L Burnett Journal: J Sex Med Date: 2010-09 Impact factor: 3.802
Authors: Haroldo A Toque; Rita C Tostes; Lin Yao; Zhimin Xu; R Clinton Webb; Ruth B Caldwell; R William Caldwell Journal: J Sex Med Date: 2010-11-03 Impact factor: 3.802
Authors: Haroldo A Toque; Maritza J Romero; Rita C Tostes; Alia Shatanawi; Surabhi Chandra; Zidonia N Carneiro; Edward W Inscho; Robert Clinton Webb; Ruth B Caldwell; Robert William Caldwell Journal: J Sex Med Date: 2010-08-30 Impact factor: 3.802