Possible Involvement of "Phosphatidylinositol-3 kinase and endothelial nitric oxide synthase' in experimental obesity induced vascular endothelium dysfunction.
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Date
2013-06
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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.
Abbreviations
(Ach): Acetylcholine, (Ang-II): Angiotensin II, (BMI): Body Mass Index, (Enos): Endothelial Nitric Oxide, Synthase, (HO-1): Heme Oxygenase, (Kcl): Pottesium Cloride, (MAP): Mean Arterial Pressure, (NO): Nitric Oxide, (PI3K): Phosphatidylinositol 3-Kinase, (SNP ): Sodium Nitroprusside, (VED): Vascular Endothelium Dysfunction
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Keywords
Adipocytes, eNOS, High fat pad, Obesity, Oxidative stress, PI3K, Vascular endothelium dysfunction, YS-49.
Citation
Dubey Gargee, Sharma P L, Sharma Saurabh. Possible Involvement of "Phosphatidylinositol-3 kinase and endothelial nitric oxide synthase' in experimental obesity induced vascular endothelium dysfunction. Journal of Applied Pharmaceutical Science. 2013 June; 3(6): 52-60.