Chronic treatment with taurine ameliorates diabetes-induced dysfunction of nitric oxide-mediated neurogenic and endothelium-dependent corpus cavernosum relaxation in rats

Fundam Clin Pharmacol. 2014 Aug;28(4):394-404. doi: 10.1111/fcp.12041. Epub 2013 Jul 12.

Abstract

This study was aimed to examine the effect of chronic taurine treatment on corpus cavernosum dysfunction in diabetic rats and to investigate possible underlying mechanisms. Thirty male rats were randomized to three groups of 10 each, including control, diabetic, and taurine-treated diabetic. Diabetes was induced in rats by streptozotocin (STZ, single intraperitoneal dose of 50 mg/kg body weight). Taurine was administered orally for 12 weeks (1% w/v in drinking water) from the day on which STZ was injected. At the end of the 12th week, strips of corpus cavernosum were suspended in an organ bath system for functional studies. Nitric oxide (NO)-mediated endothelium-dependent and neurogenic corpus cavernosum relaxation were evaluated by acetylcholine (ACh, 0.1-100 μm) and electrical field stimulation (EFS, 30 V, 5 ms, 2-32 Hz), respectively. The expressions 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 in corpus cavernosum were semi-quantitatively assessed by immunohistochemistry. Induction of diabetes resulted in significant inhibition of NO-mediated endothelium-dependent and neurogenic corpus cavernosum relaxation. Furthermore, eNOS, p-eNOS, and nNOS expressions decreased significantly in diabetic rats compared to controls, while gp91(phox) , RhoA and Rho kinase expressions increased significantly. The diminished relaxation response to ACh and EFS as well as diabetes-related changes in expressions of these proteins in corpus cavernosum of diabetic rats was significantly improved by taurine. Taurine treatment improves NO-mediated relaxations of corpus cavernosum in diabetic rats probably by inhibiting NADPH oxidase/Rho kinase pathways.

Keywords: NADPH oxidase; Rho kinase; Taurine; corpus cavernosum; diabetes mellitus; nitric oxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / administration & dosage
  • Acetylcholine / pharmacology
  • Animals
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / physiopathology
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Endothelium, Vascular / metabolism
  • Male
  • NADPH Oxidases / drug effects
  • NADPH Oxidases / metabolism
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type I / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Penis / drug effects*
  • Penis / physiopathology
  • Rats
  • Rats, Wistar
  • Streptozocin
  • Taurine / administration & dosage
  • Taurine / pharmacology*
  • rho-Associated Kinases / drug effects
  • rho-Associated Kinases / metabolism

Substances

  • Taurine
  • Nitric Oxide
  • Streptozocin
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type III
  • NADPH Oxidases
  • rho-Associated Kinases
  • Acetylcholine