Effect of bis(maltolato) oxovanadium on experimental vascular endothelial dysfunction

Abstract

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.

The Novel Role of Fenofibrate in Preventing Nicotine- and Sodium Arsenite-Induced Vascular Endothelial Dysfunction in the Rat

“…Atorvastatin was shown to improve the function of vascular endothelium by reducing oxidative stress through downregulation of NADPH oxidase [54]. In addition, atorvastatin was shown to improve the integrity of vascular endothelium [29,51]. Moreover, atorvastatin was reported to prevent the development of VED by upregulating the expression and activation of eNOS and thus increasing the generation and bioavailability of NO [55].…”

“…Since eNOS is a major isoform expressed in vascular endothelium, it is suggested that the endothelial protective potential of fenofibrate may be mediated through eNOS. Accumulating evidences suggest that elevation in the level of circulating lipids impair the integrity of vascular endothelium and induces VED [50,51]. It has been shown that nicotine administration alters the lipid profile by increasing the levels of TC and TG and consequently decreasing the levels of HDL [52].…”

Cardioprotection by Vanadium Compounds Targeting Akt-Mediated Signaling

“…The BMOVinduced inhibition of PTPase may close ATP-sensitive K + channels and consequently activate eNOS to reduce oxidative stress and subsequently improve the vascular endothelial dysfunction (104). In addition, the BMOVinduced inhibition of PTPase also improved vascular endothelial dysfunction in high fat diet-induced hypercholesterolemia (105) and deoxycorticosterone acetateinduced hypertension in rats (105).…”

Effect of bis (maltolato) oxovanadium (BMOV) in uric acid and sodium arsenite-induced vascular endothelial dysfunction in rats

“…Vanadate, a compound structurally related to BMOV, has been demonstrated to reduce oxidative stress [18]. Recently, it was reported from our laboratory that BMOV has prevented diabetes mellitus, hyperhomocysteinemia, hypertension and hypercholesterolemia-induced VED [19,20]. Uric acid has been documented to increase the generation of ROS and impair the endothelial production of NO [21][22][23].…”