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Volume: 3, Issue: 6, June, 2013
DOI: 10.7324/JAPS.2013.3608



Research Article

Possible Involvement of 'Phosphatidylinositol-3 kinase and endothelial nitric oxide synthase' in experimental obesity induced vascular endothelium dysfunction


Gargee Dubey, PL Sharma and Saurabh Sharma

  Author Affiliations


Abstract

This study was designed to investigate the possible role of Phosphatidylinositol-3 kinase (PI3K) and endothelial nitric oxide synthase (eNOS) in obesity-induced vascular endothelium dysfunction. Wistar rats were fed high fat diet (HFD) for 12 weeks to induce obesity. HFD induce obesity significantly increased parameters employed viz body weight, basal metabolic index (BMI), total fat pad and lipid profile. Furthermore vascular endothelial dysfunction was assessed in terms of decrease in endothelium dependent relaxation and serum nitrate/nitrite level and increase in mean arterial blood pressure. Atorvastatin (30mg/kg,i.p.) was employed in the present study as standard drug to improve vascular endothelial dysfunction. YS-49 (1.6 mg/kg, i.p.) a specific activator of PI3K and atorvastatin in obese rats significantly improves the lipid profile and markedly improved acetylcholine induced endothelium dependent relaxation, serum nitrite/nitrate concentration and mean arterial blood pressure. However, this ameliorative effect of YS-49 has been prevented by L-NAME (25 mg/kg, i.p.), an inhibitor of eNOS. Further wortmannin (100μg/kg, i.p.),a specific PI3K inhibitor improves the anthropometric parameters and lipid profile but did not show any significant effect on acetylcholine dependent relaxation, serum nitrate/nitrite level and mean arterial blood pressure. Therefore, it may be concluded that PI3K and eNOS pathway is dysregulated in obesity induced vascular endothelial dysfunction and YS-49, a PI3K activator improves vascular endothelial function in eNOS and nitric oxide dependent manner.

Keywords:

Adipocytes, eNOS, High fat pad, Obesity, Oxidative stress, PI3K, Vascular endothelium dysfunction, YS-49.



Citation: Gargee Dubey, PL Sharma, Saurabh Sharma., Possible Involvement of "Phosphatidylinositol-3 kinase and endothelial nitric oxide synthase" in experimental obesity induced vascular endothelium dysfunction. J App Pharm Sci, 2013; 3 (06): 052- 060.


Copyright: The Author(s). This is an open access article distributed under the Creative Commons Attribution Non-Commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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