title: Pravastatin improves the impaired nitric oxide-mediated neurogenic and endothelium-dependent relaxation of corpus cavernosum in aged rats.
abstract: OBJECTIVE
  The aim of this study was to investigate the effect of pravastatin treatment on diminished corpus cavernosum (CC) function associated with aging.
  
  
  METHODS
  Male rats were divided into three groups as adult rats (12-14 weeks old), aged rats (72-80 weeks old) and aged rats given 10 mg/kg/d pravastatin in drinking water for six weeks. Blood pressure was measured by tail-cuff method. Total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides and testosterone levels were estimated in blood. Changes in expression levels of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) (Ser-1177), neuronal nitric oxide synthase (nNOS), NADPH oxidase subunit gp91(phox), Rho A and Rho kinase (ROCK2) in CC were assessed by immunohistochemistry. Nitric oxide (NO)-mediated endothelium-dependent and neurogenic CC relaxation were evaluated by acetylcholine (ACh, 0.1 nM-100 µM) and electrical field stimulation (EFS; 30 V, 5 ms, 2-32 Hz), respectively.
  
  
  RESULTS
  In aged rats, NO-mediated, both endothelium-dependent and neurogenic CC relaxation, were significantly impaired as compared to adult rats. Besides, eNOS, p-eNOS and nNOS expressions decreased significantly in CC from aged rats, while gp91(phox), RhoA and ROCK2 expressions increased significantly. The diminished relaxation in response to ACh or EFS as well as the changes in expression of these proteins in aged rats were significantly improved by pravastatin treatment.
  
  
  CONCLUSIONS
  Pravastatin improves NO-mediated CC relaxations of aged rats probably by inhibiting NADPH oxidase/Rho kinase pathways, and this effect does not seem to be associated with lipid lowering effect of this drug.
authors.affiliation: Department of Pharmacology and.
authors.forename: Selvinaz
authors.initials: S
authors.lastname: Dalaklioglu
authors.forename: Pinar
authors.initials: P
authors.lastname: Sahin
authors.forename: Arda
authors.initials: A
authors.lastname: Tasatargil
authors.forename: Ciler
authors.initials: C
authors.lastname: Celik-Ozenci
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000187:drug effects; D010410:Penile Erection / Q000187:drug effects / Q000502:physiology; D010413:Penis / Q000187:drug effects* / Q000502:physiology; D017035:Pravastatin / Q000494:pharmacology*; D017208:Rats, Wistar
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D017035:Pravastatin
keywords: Aging; NADPH oxidase; corpus cavernosum; nitric oxide; pravastatin; rho kinase