title: Resveratrol and sildenafil synergistically improve diabetes-associated erectile dysfunction in streptozotocin-induced diabetic rats.
abstract: OBJECTIVE
  Despite effective control of blood glucose levels in diabetic patients, complaints of diabetes-associated erectile dysfunction (ED) persist. Resveratrol has been indicated to possess anti-diabetic effects and therapeutic potential for ED. This study was conducted to observe the effect of resveratrol alone or in combination with sildenafil on ED in streptozotocin (STZ)-induced diabetic rats.
  
  
  METHODS
  Among 58 adult male STZ-induced (60 mg/kg) diabetic Sprague-Dawley rats, 48 STZ-induced diabetic rats were randomized equally to four groups: untreated diabetic rats, resveratrol (25mg/kg), sildenafil (5mg/kg) or resveratrol (25mg/kg) plus sildenafil (5mg/kg) through oral gavage for 8 weeks. Additionally, 12 age-matched rats were chosen as controls. Intracavernous pressure (ICP) and mean arterial blood pressure (MAP) were used to measure erectile function. The cavernous level of cyclic guanosine monophosphate (cGMP), protein and mRNA of endothelial NO synthase (eNOS), neuronal NOS (nNOS), and phosphodiesterase-5 (PDE5) was measured.
  
  
  RESULTS
  Treatment with either resveratrol or sildenafil improved ICP/MAP compared to the untreated diabetic rats (P<0.05). Treatment with resveratrol increased nNOS and eNOS expression, inhibited PDE5 expression, and increased the cavernous cGMP level compared to the untreated diabetic rats. Resveratrol significantly decreased superoxide anion and ROS production. Two-way ANOVA indicated that resveratrol in combination with sildenafil therapy had a significant synergistic effect in improving ICP/MAP and cavernous cGMP levels.
  
  
  CONCLUSIONS
  Resveratrol improves diabetes-associated ED in rats. Combination therapies with resveratrol and sildenafil have a synergistic effect in improving ED. The mechanisms might be attributed to its anti-oxidative properties and NO-cGMP signaling pathway upregulation.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Electronic address: anruihua62@163.com.
authors.forename: Ruihua
authors.initials: R
authors.lastname: An
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000378:metabolism; D048909:Diabetes Complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007172:Erectile Dysfunction / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D051381:Rats; D000077185:Resveratrol; D015290:Second Messenger Systems / Q000187:drug effects; D000068677:Sildenafil Citrate; D013267:Stilbenes / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013267:Stilbenes; D013449:Sulfonamides; D000068677:Sildenafil Citrate; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496316:Nos3 protein, rat; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006152:Cyclic GMP; D000077185:Resveratrol
keywords: Diabetes mellitus; Erectile dysfunction; NO–cGMP; Reactive oxygen species; Resveratrol; Superoxide anion