Shah Dhvanit I, Singh Manjeet
Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala, 147002, Punjab, India.
Naunyn Schmiedebergs Arch Pharmacol. 2006 Jun;373(3):221-9. doi: 10.1007/s00210-006-0066-1. Epub 2006 May 3.
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.
本研究旨在探究蛋白质酪氨酸磷酸酶抑制剂双（麦芽醇）氧钒（BMOV）对高胆固醇血症和高血压诱导的血管内皮功能障碍的影响。分别给大鼠喂食高脂饮食（8周）和皮下注射醋酸脱氧皮质酮（DOCA；40 mg kg⁻¹）以诱导高胆固醇血症和高血压（平均动脉血压>120 mmHg）。使用离体主动脉环标本、胸主动脉电子显微镜检查以及血清亚硝酸盐/硝酸盐浓度来评估血管内皮功能障碍。通过测定血清硫代巴比妥酸反应性物质（TBARS）来评估氧化应激。BMOV（饮用水中浓度为0.2 mg/ml）或阿托伐他汀（30 mg kg⁻¹，口服）可显著改善高胆固醇血症和高血压大鼠中乙酰胆碱诱发的内皮依赖性舒张、血管内皮衬里、血清亚硝酸盐/硝酸盐浓度以及血清TBARS。然而，NOS抑制剂L-NAME（25 mg kg⁻¹，腹腔注射）或ATP敏感性钾通道阻滞剂格列本脲（5 mg kg⁻¹，腹腔注射）可阻止BMOV的这种改善作用。可以得出结论，BMOV诱导的PTPase抑制作用可能改善血管内皮功能障碍。
