The effect of N-acetylcysteine on cardiac contractility to dobutamine in rats with streptozotocin-induced diabetes

Eur J Pharmacol. 2005 Sep 5;519(1-2):118-26. doi: 10.1016/j.ejphar.2005.06.037.

Abstract

We examined if myocardial depression at the acute phase of diabetes (3 weeks after injection of streptozotocin, 60 mg/kg i.v.) is due to activation of inducible nitric oxide synthase and production of peroxynitrite, and if treatment with N-acetylcysteine (1.2 g/day/kg for 3 weeks, antioxidant) improves cardiac function. Four groups of rats were used: control, N-acetylcysteine-treated control, diabetic and N-acetylcysteine-treated diabetic. Pentobarbital-anaesthetized diabetic rats, relative to the controls, had reduced left ventricular contractility to dobutamine (1-57 microg/min/kg). The diabetic rats also had increased myocardial levels of thiobarbituric acid reactive substances, immunostaining of inducible nitric oxide synthase and nitrotyrosine, and similar baseline 15-F2t-isoprostane. N-acetylcysteine did not affect responses in the control rats; but increased cardiac contractility to dobutamine, reduced myocardial immunostaining of inducible nitric oxide synthase and nitrotyrosine and level of 15-F2t-isoprostane, and increased cardiac contractility to dobutamine in the diabetic rats. Antioxidant supplementation in diabetes reduces oxidative stress and improves cardiac function.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Animals
  • Antioxidants / metabolism
  • Blood Glucose / metabolism
  • Blood Pressure / drug effects
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / physiopathology*
  • Dinoprost / analogs & derivatives
  • Dinoprost / metabolism
  • Dobutamine / pharmacology*
  • Dose-Response Relationship, Drug
  • Heart Rate / drug effects
  • Immunohistochemistry
  • Male
  • Myocardial Contraction / drug effects*
  • Myocardium / metabolism
  • Nitric Oxide Synthase / analysis
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Rats
  • Rats, Wistar
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Tyrosine / analogs & derivatives
  • Tyrosine / analysis

Substances

  • Antioxidants
  • Blood Glucose
  • Thiobarbituric Acid Reactive Substances
  • 8-epi-prostaglandin F2alpha
  • 3-nitrotyrosine
  • Dobutamine
  • Tyrosine
  • Dinoprost
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos2 protein, rat
  • Nos3 protein, rat
  • Acetylcysteine