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Effect of angiotensin II on energetics, glucose metabolism and cytosolic NADH/NAD and NADPH/NADP redox in vascular smooth muscle

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Abstract

Angiotensin II (AII) is a neurohormone and contractile agonist of vascular smooth muscle that has been shown to be involved in the pathogenesis of vascular disease, which may be partially caused by its effect on oxidant stress. Energy metabolism was examined in pig carotid arteries treated with AII, because the activity of pathways of intermediary metabolism of glucose determines the status of cytosolic NADH/NAD and NADPH/NADP redox, factors which are involved in oxidant stress. Contractile responses to AII were characterized by an increase in isometric force followed by a gradual decline to near-basal levels. Despite contractile activation, no change in glycolysis, lactate production, glucose oxidation, fatty acid oxidation, O2 consumption, glycogen content or high-energy phosphates was detected when compared to resting unstimulated arteries. Paradoxically, total uptake of glucose was inhibited by AII. Treatment with diphenylene iodinium, an inhibitor of NAD(P)H oxidase and superoxide production, reversed the inhibition of glucose uptake and revealed the expected increase in glucose uptake and oxidation upon contractile activation of smooth muscle by AII. The intracellular [lactate]/pyruvate] ratio was increased, reflecting an increase in cytosolic NADH/NAD redox, whereas NADPH/NADP redox was decreased by AII. No change in NADPH/NADP redox was observed when membrane depolarization with K+ was used as the contractile agent. It is concluded that the pattern of force generation, metabolism and energetics of AII-stimulated contraction are significantly different from that of other contractile agonists. Most notably AII inhibited glucose uptake. NAD(P)H oxidase and/or attendant superoxide may play a role in modulating glucose metabolism. AII induces opposite changes in NADH/NAD redox and NADPH/NADP redox, which may have important consequences for oxidant stress. (Mol Cell Biochem 262: 91–99, 2004)

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  1. Division of Cardiology, Department of Internal Medicine, Rush Medical College, Rush University Medical Center, Chicago, IL, USA

    John T. Barron, Mark F. Sasse & Aisha Nair

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Barron, J.T., Sasse, M.F. & Nair, A. Effect of angiotensin II on energetics, glucose metabolism and cytosolic NADH/NAD and NADPH/NADP redox in vascular smooth muscle. Mol Cell Biochem 262, 91–99 (2004). https://doi.org/10.1023/B:MCBI.0000038221.44904.a1

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