title: Poly(ADP-ribose) polymerase inhibition improves erectile function by activation of nitric oxide/cyclic guanosine monophosphate pathway in diabetic rats.
abstract: BACKGROUND
  Endothelial dysfunction-induced abnormalities of the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway in the corpus cavernosum are thought to be the main factors involved in the pathogenesis of diabetes-induced erectile dysfunction (ED). Recent studies have shown that the poly(adenosine diphosphate ribose) polymerase (PARP) pathway plays a critical role in diabetic endothelial dysfunction.
  
  
  OBJECTIVE
  The aim of this study is to determine whether activation of the PARP pathway is involved in diabetic cavernosal endothelial dysfunction and abnormalities of the NO/cGMP pathway.
  
  
  METHODS
  Male Sprague-Dawley rats were randomly divided into three groups: age-matched controls, diabetic controls (DM), and the 3-aminobenzamide (3-AB, a PARP inhibitor)-treated diabetic group (DM+3-AB). Diabetes was induced by intraperitoneal injection of streptozotocin. Eight weeks after inducing diabetes, the DM+3-AB group was treated with 3-AB for 4 weeks.
  
  
  METHODS
  Erectile function was assessed at 12 weeks after inducing diabetes by stimulating the cavernous nerve. Expression of poly(ADP-ribose), protein kinase B (Akt), phospho-Akt, endothelial nitric oxide synthase (eNOS), phospho-eNOS, and neuronal nitric oxide synthase (nNOS) were evaluated by Western blot. Cavernous NO generation and cGMP levels were also determined.
  
  
  RESULTS
  The DM group showed impaired erectile function and significantly increased PARP activity. Expression of total eNOS and nNOS, phospho-Akt, and eNOS decreased significantly in the DM group compared with those in the control group. In addition, cavernous NO generation and cGMP levels decreased significantly in the DM group compared with those in the control group. Treatment with 3-AB restored erectile function and significantly reversed all molecular alterations except decreased nNOS expression.
  
  
  CONCLUSIONS
  Overactivation of the PARP pathway in the corpus cavernosum of diabetic rats was involved in cavernosal endothelial dysfunction and abnormalities of the NO/cGMP pathway resulting in ED. These findings may be applied to develop novel therapies for patients with diabetic ED.
authors.affiliation: Department of Urology and Andrology, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. wenjili@naver.com
authors.forename: Wen Ji
authors.initials: WJ
authors.lastname: Li
authors.forename: YuBing
authors.initials: Y
authors.lastname: Peng
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.forename: Bao
authors.initials: B
authors.lastname: Li
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D015153:Blotting, Western; D006152:Cyclic GMP / Q000032:analysis / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I / Q000032:analysis / Q000502:physiology; D052250:Nitric Oxide Synthase Type III / Q000032:analysis / Q000502:physiology; D010410:Penile Erection / Q000187:drug effects / Q000502:physiology*; D010413:Penis / Q000737:chemistry; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009569:Nitric Oxide; C025160:3-aminobenzamide; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D011065:Poly(ADP-ribose) Polymerases; D006152:Cyclic GMP