Apocynin restores endothelial dysfunction in streptozotocin diabetic rats through regulation of nitric oxide synthase and NADPH oxidase expressions

OLUKMAN M. , ORHAN C. E. , Celenk F. G. , ULKER S.

JOURNAL OF DIABETES AND ITS COMPLICATIONS, vol.24, no.6, pp.415-423, 2010 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 24 Issue: 6
  • Publication Date: 2010
  • Doi Number: 10.1016/j.jdiacomp.2010.02.001
  • Page Numbers: pp.415-423


Aim: Increased production of reactive oxygen species (ROS) in the diabetic vasculature results in the impairment of nitric oxide (NO)mediated relaxations leading to impaired endothelium-dependent vasodilation. An important source of ROS is nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and the inhibition of this enzyme is an active area of interest. This study aimed to investigate the effects of apocynin, an NADPH oxidase inhibitor, on endothelial dysfunction and on the expression of NO synthase (NOS) and NADPH oxidase in thoracic aorta of diabetic rats. Method: Streptozotocin (STZ)-diabetic rats received apocynin (16 mg/kg per day) for 4 weeks. Endothelium-dependent and -independent relaxations were determined in thoracic aortic rings. Western blotting and RT-PCR analysis were performed for NOSs and NADPH oxidase in the aortic tissue. Results: Acetylcholine-induced relaxations and L-NAME-induced contractions were decreased in diabetic aorta. The decrease in acetylcholine and L-NAME responses were prevented by apocynin treatment without a significant change in plasma glucose levels. Endothelial NOS (eNOS) protein and mRNA expression exhibited significant decrease in diabetes, while protein and/or mRNA expressions of inducible NOS (iNOS) as well as p22(phox) and gp91(phox) subunits of NADPH oxidase were increased, and these alterations were markedly prevented by apocynin treatment. Conclusion: NADPH oxidase expression is increased in diabetic rat aorta. NADPH oxidase-mediated oxidative stress is accompanied by the decreased eNOS and increased iNOS expressions, contributing to endothelial dysfunction. Apocynin effectively prevents the increased NADPH oxidase expression in diabetic aorta and restores the alterations in NOS expression, blocking the vicious cycle leading to diabetes-associated endothelial dysfunction. (C) 2010 Elsevier Inc. All rights reserved.