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Role of GLUT4 on angiotensin 2-induced systemic and renal hemodynamics

Authors Igbe I, Omogbai, Oyekan

Received 2 June 2012

Accepted for publication 11 August 2012

Published 8 April 2013 Volume 2013:5 Pages 1—13

DOI https://doi.org/10.2147/JEP.S34583

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

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Ighodaro Igbe,1 Eric Kelly I Omogbai,1 Adebayo O Oyekan2

1Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin, Nigeria; 2Center for Cardiovascular Diseases, College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas, USA

Abstract: Cross-talk between insulin and the renin angiotensin system signaling system shows that angiotensin 2 (A2) negatively modulates insulin signaling by stimulating multiple serine phosphorylation events in the early stages of the insulin-signaling cascade; however, the biological actions of A2 on insulin sensitivity remain controversial. Preservation of glucose transporter 4 (GLUT4) expression during hypertension has been shown to prevent the increased vascular reactivity associated with hypertension. This study tested the hypothesis that GLUT4 contributes to the renal actions of A2. In the euvolemic anesthetized rat, acute infusion of the GLUT4 antagonist, indinavir (1 mg/kg/minute), enhanced an A2-induced increase in mean arterial blood pressure (MABP) (P < 0.01), but attenuated an A2-induced increase in medullary blood flow (MBF) and glomerular filtration rate (P < 0.01). Insulin, a GLUT4 activator (20 mU/kg/minute and 40 mU/kg/minute), decreased basal MABP and urine volume (P < 0.05), but it increased MBF, and these effects were reversed and blunted by indinavir. Subchronic indinavir treatment (80 mg/kg/day orally for 15 days) did not affect A2-induced changes in MABP, cortical blood flow, and MBF, but significantly decreased basal MBF (P < 0.01) and global kidney perfusion (P < 0.05). We concluded that acute but not subchronic inhibition of GLUT4 alters A2-induced changes in systemic and renal hemodynamics by attenuating A2-induced increase in MBF and glomerular filtration rate.

Keywords: angiotensin 2, indinavir, hemodynamics, GLUT4, medullary blood flow

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