title: Improvement in erectile function in a rat model of high cholesterol diet-induced atherosclerosis by atorvastatin in a manner that is independent of its lipid-lowering property.
abstract: The purpose of the present study is to explore the effects of a lipid-lowering drug atorvastatin, a three-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, in the treatment of erectile dysfunction (ED) in a rat model of atherosclerosis (AS) and the possible mechanisms underneath. A high-cholesterol diet was administrated to Sprague-Dawley rats in an attempt to induce an ASED model, which was later confirmed by abdominal aorta histopathology and erectile function evaluation. ASED rats were further assigned to non-treatment group, atorvastatin low-dose treatment group (5 mg kg-1day-1), high-dose group (10 mg kg-1day-1) and sildenafil (1.5 mg kg-1day-1) treatment group. Lipid profile, erectile function, oxidative stress biochemical markers, endothelial nitric oxide synthase (eNOS) and extracellular superoxide dismutase (SODEX) mRNA expression were evaluated after 8-week treatment duration. Erectile function was impaired in AS rat model, which was preserved in atorvastatin and sildenafil intervention groups. The oxidative stress biochemical markers were attenuated, while eNOS and SODEXmRNA expression were restored in atorvastatin and sildenafil groups, which were found to be involved in ED pathogenesis. However, the lipid profile remained unaltered in the treatment group, and it was elevated in ASED rats. This kind of lipid-lowering agent, or atorvastatin, has the utilisation potential in ASED treatment, even before lipid profiles altered. This effect on erectile function preservation of atorvastatin was attributed to its preservation of endothelial function, possibly through amelioration of oxidative stress and improvement in eNOS expression.
authors.affiliation: Department of Andrology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Jiangsu University, Zhenjiang, China.
authors.forename: L
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Andrology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: W
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Andrology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Andrology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Y-T
authors.initials: YT
authors.lastname: Dai
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy*; D000069059:Atorvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000187:drug effects; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010413:Penis / Q000187:drug effects / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069059:Atorvastatin; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D013482:Superoxide Dismutase
keywords: atherosclerosis; atorvastatin; erectile dysfunction; lipid profile; statins