Effect of bis(maltolato) oxovanadium on experimental vascular endothelial dysfunction.
The study has been designed to investigate the effect of bis(maltolato) oxovanadium (BMOV), a protein tyrosine phosphatase inhibitor, on hypercholesterolemia and hypertension-induced vascular endothelial dysfunction. High fat diet (8 weeks) and deoxycorticosterone acetate (DOCA; 40 mg kg(-1), s.c.) were administered to rats to produce hypercholesterolemia and hypertension (mean arterial blood pressure >120 mmHg) respectively. Vascular endothelial dysfunction was assessed using isolated aortic ring preparation, electron microscopy of thoracic aorta, and serum concentration of nitrite/nitrate. Serum thiobarbituric acid reactive substances (TBARS) were estimated to assess oxidative stress. BMOV (0.2 mg/ml in drinking water) or atorvastatin (30 mg kg(-1), p.o.) markedly improved acetylcholine-evoked endothelium-dependent relaxation, lining of vascular endothelium, serum nitrite/nitrate concentration, and serum TBARS in hypercholesterolemic and hypertensive rats. However, this ameliorative effect of BMOV has been prevented by L-NAME (25 mg kg(-1), i.p.), an inhibitor of NOS, or by glibenclamide (5 mg kg(-1), i.p.), a blocker of ATP-sensitive K(+) channels. It may be concluded that BMOV-induced inhibition of PTPase may improve vascular endothelial dysfunction.
Shah
Dhvanit I
DI
Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala, 147002, Punjab, India.
Singh
Manjeet
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016232:Endothelins / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008855:Microscopy, Electron, Scanning; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D011753:Pyrones / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology / Q000627:therapeutic use*; D014652:Vascular Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects
D016232:Endothelins; D009566:Nitrates; D009573:Nitrites; D011753:Pyrones; D017392:Thiobarbituric Acid Reactive Substances; C074212:bis(maltolato)oxovanadium(IV); D014638:Vanadates