Vanadyl sulfate lowers plasma insulin and blood pressure in spontaneously hypertensive rats.

Bhanot, Sanjay; McNeill, John H.

doi:10.1161/01.hyp.24.5.625

Cited by 68 publications

(24 citation statements)

References 42 publications

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“…In addition, we recently introduced a novel vanadyl (IV) compound having V O 2ϩ chelate, bis(1-oxy-2-pyridinethiolato) oxovanadium (IV), [VO[(OPT)], as potent activator of protein kinase B/Akt, thereby protecting cardiomyocytes from ischemia/ reperfusion injury in rats 18 and in mouse brain ischemia. 21 Consistent with our findings, the vanadyl (IV) form of vanadium possesses cardioprotective action 22 and antihypertensive action in spontaneous hypertensive rats and in fructose-induced hypertensive rats [23][24][25] through unknown mechanisms.…”

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confidence: 84%

Activation of Endothelial Nitric Oxide Synthase by a Vanadium Compound Ameliorates Pressure Overload-Induced Cardiac Injury in Ovariectomized Rats

et al. 2009

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Abstract-We here investigated the effect of bis(1-oxy-2-pyridinethiolato) oxovanadium (IV), [VO(OPT)], against myocardial hypertrophy and cardiac functional recovery in pressure overload-induced hypertrophy in ovariectomized female rats and defined mechanisms underlying its cardioprotective action. Wistar rats subjected to bilateral ovariectomy were further treated with abdominal aortic stenosis. VO(OPT) (containing 1.25 and 2.50 mg of vanadium per kg) was administered orally once a day for 14 days starting from 2 weeks after aortic banding. Treatment with VO(OPT) significantly inhibited pressure overload-induced increase both in the heart weight:body weight ratio and the lung weight:body weight ratio. VO(OPT) also attenuated hypertrophy-induced impaired left ventricular end-diastolic pressure, left ventricular developed pressure, and left ventricular contractility (Ϯdp/dt max ). VO(OPT) treatment significantly restored pressure overload-induced impaired endothelial NO synthase activity with concomitant increased phosphorylation of endothelial NO synthase (Ser1179). Moreover, VO(OPT) treatment significantly restored pressure overload-induced reduced Akt activity, as indicated by increased phosphorylation at Ser473 and at Thr308. Treatment with VO(OPT) also secondarily inhibited calpastatin and dystrophin breakdown and decreased myosin light chain phosphorylation. Finally, VO(OPT) treatment significantly attenuated mortality after repeated isoproterenol administration in pressure overloaded-ovariectomized rats. Taken together, VO(OPT) attenuates cardiac myocytes hypertrophy in vivo in pressure overload-induced hypertrophy in ovariectomized rats and prevents the process from hypertrophy to heart failure. These effects are mediated by inhibition of calpastatin and dystrophin breakdown in addition to increased Akt and endothelial NO synthase activities. Key Words: myocardial hypertrophy Ⅲ protein kinase B (Akt) Ⅲ endothelial nitric oxide synthase (eNOS) Ⅲ ovariectomy Ⅲ dystrophin L eft ventricular (LV) hypertrophy is an independent risk factor for the development of heart failure. 1 Although LV hypertrophy is an adaptive response to pressure and volume overload, this process becomes maladaptive without drug therapy. The pathological cardiac hypertrophy, in turn, triggers the development of heart failure. 2 The search for novel drug treatment has directed attention to cardiac hypertrophy as cardioprotection. 2 Signaling through the phosphatidylinositol 3-kinase/Akt pathway is important for the physiological growth and inhibition of pathological hypertrophy. 3-5 Moreover, physiological hypertrophy induced by exercise training also requires the activation of myocardial Akt. By contrast, pathological hypertrophies induced by pressure overload cause an inactivation of the Akt signal pathway. 6 We have also reported that pressure overload (PO)-induced hypertrophy in ovariectomized (OVX) female rats markedly reduces both endothelial NO synthase (eNOS) protein expression and its activity with concomitantly marked reduced Ak...

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confidence: 84%

Activation of Endothelial Nitric Oxide Synthase by a Vanadium Compound Ameliorates Pressure Overload-Induced Cardiac Injury in Ovariectomized Rats

et al. 2009

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“…Until now, four vanadium compounds, namely, sodium orthovanadate (OV) (42,43); vanadyl sulfate (VS) (20,22,30); bis(maltolato)oxovanadium (IV) [BMOV] (21,44,45); and VO(OPT) (18,19,28), have been found to have cardioprotective effects in different heart injury models (Fig. 1).…”

Section: Akt Activator Vanadium Compounds For Treatment Of Cardiac DImentioning

confidence: 99%

“…Among these, the cardioprotective effects of vanadium has been studied in great detail, and several studies have demonstrated that the vanadyl (IV) form of vanadium possesses cardioprotective properties (15) in diabetic rats (16,17), myocardial ischemia /reperfusion-induced injury in rats (18,19), spontaneously hypertensive rats (SHR) (20,21), and fructose-fed rats (22), representing a genetic and dietinduced model of hypertension (23). Among the several oxidation states of vanadium II to V, vanadium ion in living cells exists exclusively as vanadyl (IV) cation and a small amount of vanadate (V) anion (24).…”

Section: Introductionmentioning

confidence: 99%

Cardioprotection by Vanadium Compounds Targeting Akt-Mediated Signaling

Bhuiyan

Fukunaga

2009

J Pharmacol Sci

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Abstract. Treatment with inorganic and organic compounds of vanadium has been shown to exert a wide range of cardioprotective effects in myocardial ischemia/reperfusion-induced injury, myocardial hypertrophy, hypertension, and vascular diseases. Furthermore, administration of vanadium compounds improves cardiac performance and smooth muscle cell contractility and modulates blood pressure in various models of hypertension. Like other vanadium compounds, we documented bis(1-oxy-2-pyridinethiolato) oxovanadium (IV) [VO(OPT)] as a potent cardioprotective agent to elicit cardiac functional recovery in myocardial infarction and pressure overload-induced hypertrophy. Vanadium compounds activate Akt signaling through inhibition of protein tyrosine phosphatases, thereby eliciting cardioprotection in myocardial ischemia / reperfusion-induced injury and myocardial hypertrophy. Vanadium compounds also promote cardiac functional recovery by stimulation of glucose transport in diabetic heart. We here discuss the current understanding of mechanisms underlying vanadium compound-induced cardioprotection and propose a novel therapeutic strategy targeting for Akt signaling to rescue cardiomyocytes from heart failure.

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“…24 However, vanadate (in 40 to 80 mol/L range) may also promote endothelium-dependent vasodilation, 30 may reduce systolic blood pressure in spontaneously hypertensive rats 31 and may also ameliorate the exaggerated vasoconstriction in aortic tissue from the hyperinsulinemic/ insulin-resistant obese Zucker rat. 32 McNeill and coworkers 31,33,34 have shown that long-term vanadium treatment of insulin-resistant/diabetic rats led to reduction in BP, perhaps related to normalization of metabolic alterations in the insulin-resistant and diabetic state by vanadium compounds. The changes in erythrocyte Mg i levels may be intimately linked to changes in erythrocyte Ca i levels.…”

Section: Discussionmentioning

confidence: 99%

Insulin-Mimetic Action of Vanadate

2001

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Abstract-The insulin-mimetic effect of vanadate is well established, and vanadate has been shown to improve insulin sensitivity in diabetic rats and humans. Although the exact mechanism(s) remain undefined, we have previously demonstrated a direct relation of intracellular free magnesium (Mg i ) levels to glucose disposal, to insulinemic responses following glucose loading, and to insulin-induced ionic effects. To investigate whether the insulin-mimetic effects of vanadate could similarly be mediated by Mg i , we utilized 31 P-nuclear magnetic resonance spectroscopy to measure Mg i in erythrocytes from normal (NL, nϭ10) and hypertensive (HTN, nϭ12) Key Words: magnesium Ⅲ vanadate Ⅲ insulin Ⅲ nuclear magnetic resonance spectroscopy T he phosphatase inhibitor vanadate is a compound that has insulin-mimetic properties both in vitro and in vivo, and it has been proposed in the treatment of diabetes mellitus. 1 As such, vanadate lowers plasma glucose levels, increases peripheral glucose uptake, and improves insulin sensitivity. 1,2 Depletion of another mineral ion, intracellular free magnesium (Mg i ), is a characteristic feature of insulin resistance in essential hypertension and type 2 diabetes mellitus, but it is not clear to what extent lower Mg i levels contribute to insulin resistance, result from it, or both. Abnormalities of Mg i and cytosolic free calcium (Ca i ) have been closely related to the level of blood pressure, the extent of cardiac hypertrophy, and the degree of insulin resistance present in these clinical states. [3][4][5][6] Our group has proposed that the insulin resistance of hypertension and type 2 diabetes mellitus results, at least in part, from an ionic defect characterized by cellular Mg i deficiency and cellular Ca i accumulation. [5][6][7] We have previously demonstrated a direct relation of Mg i levels to glucose disposal, to insulinemic responses following glucose loading, and to insulin-induced stimulation of Mg i . [5][6][7][8] Conversely, because the ability of insulin-like growth factor I (IGF-I) to improve insulin sensitivity may depend on its stimulation of Mg i , 9 we wondered whether the ability of vanadate to improve insulin action was also linked to cellular magnesium metabolism.We therefore utilized 31 P-nuclear magnetic resonance (NMR) spectroscopic techniques to assess Mg i responses to vanadate compared with insulin in erythrocytes from normotensive and essential hypertensive individuals. Subjects and MethodsTwenty milliliters of venous blood were drawn from unmedicated normotensive (nϭ10, male/femaleϭ5/5) and hypertensive (nϭ12, male/femaleϭ7/5) subjects in the morning (9:00 AM to noon) after an overnight fast. Previous medications were withdrawn for at least 3 weeks; diuretics, for at least 3 months before study. Essential hypertension was diagnosed on the basis of at least 3 blood pressure readings Ͼ150/90 mm Hg in the absence of signs or symptoms of secondary forms of hypertension. A history of myocardial infarction, angina pectoris, or stroke in the last 6 months b...

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Vanadyl sulfate lowers plasma insulin and blood pressure in spontaneously hypertensive rats.

Cited by 68 publications

References 42 publications

Activation of Endothelial Nitric Oxide Synthase by a Vanadium Compound Ameliorates Pressure Overload-Induced Cardiac Injury in Ovariectomized Rats

Activation of Endothelial Nitric Oxide Synthase by a Vanadium Compound Ameliorates Pressure Overload-Induced Cardiac Injury in Ovariectomized Rats

Cardioprotection by Vanadium Compounds Targeting Akt-Mediated Signaling

Insulin-Mimetic Action of Vanadate

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