Abstract
Although considerable evidence lends credence to the association between insulin resistance, hyperinsulinemia and essential hypertension, the precise nature of this relationship remains unexplained. In the present investigation, we examined the proposition that these metabolic defects contribute causally to the development of high blood pressure. If these metabolic abnormalities were responsible for the development of hypertension, then drug interventions that improve these defects should also decrease high blood pressure. Since previous studies have demonstrated that vanadium compounds enhance insulin action and lower plasma insulin levels in nondiabetic rats, we examined the effects of these compounds on insulin sensitivity, plasma insulin concentration and blood pressure in two hyperinsulinemic models of experimental hypertension. The animal models studied were the genetically predisposed spontaneously hypertensive rat and the fructose-hypertensive rat, where hypertension is induced in normotensive rats by feeding them a high fructose diet. Vanadium compounds caused marked and sustained decreases in plasma insulin concentration and blood pressure in both the animal models studied. Furthermore, the effect of the drugs on blood pressure was reversed by restoring plasma insulin levels in the drug-treated rats to those observed in their untreated counterparts. These data suggest that either hyperinsulinemia contributes to the development of hypertension in both the spontaneously hypertensive and the fructose-hypertensive rats or that the underlying mechanism is closely related to the expression of both these disorders.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
DeFronzo RA, Ferrannini E: Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia and atherosclerotic cardiovascular disease. Diabetes Care 14: 173–194, 1991
Ferrannini E, Natali A: Essential hypertension, metabolic disorders and insulin resistance. Am Heart J 121: 1274–1282, 1991
Reaven GM: Role of insulin resistance in human disease. Diabetes 37: 1595–1607, 1988
Modan M, Halkin H, Almog S, Lusky A, Eskol A, Shefi M, Shitrit A, Fucho I: Hyperinsulinemia: a link between hypertension, obesity and glucose intolerance. J Clin Invest 75: 809–417, 1985
Bonora E, Zavaroni I, Pezarossa A, Alpi O, Brushi F, Dall'Aglio E, Guerra L, Coscelli C, Butturini U: Relationship between blood pressure and plasma insulin in nonobese and obese nondiabetic subjects. Diabetologia 30: 719–723, 1987
Pollare T, Lithell H, Berne C: Insulin resistance is a characteristic feature of primary hypertension independent of obesity. Metabolism 39: 167–174, 1990
Haffner SM, Fong D, Hazuda HP, Pugh JA, Patterson JK: Hyperinsulinemia, upper body adiposity and cardiovascular risk factors in non-diabetics. Metabolism 37: 338–345, 1988
Ferrannini E, Buzzigoli G, Bonadonna R, Giorico MA, Oleggini M, Graziadei L, Pedrinelli R, Brandi L, Bevilacqua S: Insulin resistance in essential hypertension. N Eng J Med 317: 350–354, 1987
Shechter Y: Insulin-mimetic effects of vanadate: possible implications for future treatment of diabetes. Diabetes 39: 1–5, 1990
Duckworth WC, Solomon SS, Loiepnieks J, Hamel FG, Hand S, Peavy DE: Insulin like effects of vanadate in isolated rat adipocytes. Endocrinology 122: 2285–2289, 1988
Clark AS, Fagan JM, Mitch WE: Selectivity of the insulin-like action of vanadate on glucose and protein metabolism in skeletal muscle. Biochem J 232: 273–276, 1985
Dubyak GR, Kleinzeller A: The insulin-mimetic effects of vanadate in isolated rat adipocytes. Dissociation from effects of vanadate as (Na/K)ATPase inhibitor. J Biol Chem 255: 5306–5312, 1980
Degani H, Gochin M, Karlish SJD, Shechter Y: Electron paramagnetic studies and insulin-like effects of vanadium in rat adipocytes. Biochemistry 20: 5795–5799, 1981
Shechter Y, Ron A: Effect of depletion of phosphate and bicarbonate ions on insulin action in rat adipocytes. J Biol Chem 261: 1494–14950, 1986
Heyliger CE, Tahiliani AG, McNeill JH: Effect of vanadate on elevated blood glucose and depressed cardiac performance of diabetic rats. Science 227: 1474–1477, 1985
Ramanadham S, Mongold JJ, Brownsey RW, Cros GH, McNeill JH: Oral vanadyl sulphate in the treatment of diabetes mellitus in the rat. Am J Physiol 257: H904-H911, 1989
Ramanadham S, Cros GH, Mongold JJ, Serrano JJ, McNeill JH: Enhanced in vivo sensitivity of vanadyl treated diabetic rats to insulin. Can J Physiol Pharmacol 68: 486–491, 1990
Mondon CE, Reaven GM: Evidence of abnormalities of insulin metabolism in rats with spontaneous hypertension. Metabolism 37: 303–305, 1988
Hwang IS, Ho H, Hoffman BB, Reaven GM: Fructose induced insulin resistance and hypertension in rats. Hypertension 10: 512–516, 1987
Diebert DC, DeFronzo RA: Epinephrine induced insulin resistance in man: a beta receptor mediated phenomenon. J Clin Invest 65: 717–721, 1980
Swislocki ALM, Hoffman BB, Reaven GM: Insulin resistance, glucose intolerance and hyperinsulinemia in patients with hypertension. Am J Hypert 2: 419–423, 1989
Shen DC, Shieh SM, Fuh MMT, Wu DA, Chen YDI, Reaven GM: Resistance to insulin stimulated glucose uptake in patients with hypertension. J Clin Endocrinol Metab 66: 580–583, 1988
Hulman S, Falkner B, Chen YQ: Insulin resistance in the spontaneously hypertensive rat. Metabolism 40: 359–361, 1991
Mondon CE, Reaven GM, Azhar S, Lee CM, Rabkin R: Abnormal insulin metabolism by specific organs from rats with spontaneous hypertension. Am J Physiol 257: E491-E498, 1989
Buchanan TA, Sipos GF, Madrilejo N, Chaplin L, Campese VM: Hypertension without peripheral insulin resistance in spontaneously hypertension rats. Am J Physiol 262:E14-E19, 1992
Buchanan TA, Youn JH, Campese VM, Sipos GM: Enhanced glucose tolerance in spontaneously hypertensive rats: pancreatic β cell hyperfunction with normal insulin sensitivity. Diabetes 41:872–878, 1992
Bhanot S, McNeill JH: Vanadyl sulfate lowers plasma insulin levels and blood pressure in spontaneously hypertensive rats. Hypertension 24: 625–632, 1994
Conklin AW, Skinner TL, Fetin TL, Sanders CL: Clearance and distribution of intratracheally instilled vanadium-48 compounds in the rat. Toxicol Letter 11:199–203, 1982
Underwood EJ: In “Trace elements in human and animal nutrition” Academic Press, New York, pp 388–397, 1977
McNeill JH, Yuen VG, Hoveyda HR, Orvig C: Bis(maltolato)oxovanadium(IV) is a potent insulin mimic. J Med Chem 35: 1489–1491, 1992
Bhanot S, Bryer-Ash M, Cheung A, McNeill JH: Bis(maltolato)-oxovanadium(IV) attenuates hyperinsulinemia and hypertension in spontaneously hypertensive rats. Diabetes 43:857–861, 1994
Cros GC, Mongold JJ, Serrano JJ, Ramanadham S, McNeill JH: Effects of vanadyl derivatives on animal models of diabetes. Mol Cell Biochem 109:163–166, 1992
Hwang IS, Huang WC, Wu JN, Shian LR, Reaven GM: Effect of fructose induced hypertension on the renin-angiotensin-aldosterone system and atrial natriuretic factor. Am J Hypert 2:424–427, 1989
Reaven GM, Ho H, Hoffman BB: Attenuation of fructose induced hypertension in rats by exercise training. Hypertension 12:129–32, 1988
Ho H, Hoffman BB: Somatostatin inhibition of fructose induced hypertension. Hypertension 14:117–120, 1989
Bhanot S, McNeill JH, Bryer-Ash M: Vanadyl sulfate prevents fructose-induced hyperinsulinemia and hypertension in rats. Hypertension 23:308–312, 1994
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bhanot, S., Michoulas, A. & McNeill, J.H. Antihypertensive effects of vanadium compounds in hyperinsulinemic, hypertensive rats. Mol Cell Biochem 153, 205–209 (1995). https://doi.org/10.1007/BF01075939
Issue Date:
DOI: https://doi.org/10.1007/BF01075939