title: Role of GLUT4 on angiotensin 2-induced systemic and renal hemodynamics.
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.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin, Nigeria.
authors.forename: Ighodaro
authors.initials: I
authors.lastname: Igbe
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin, Nigeria.
authors.forename: Eric Kelly
authors.initials: EK
authors.lastname: Omogbai
authors.affiliation: Center for Cardiovascular Diseases, College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas, USA.
authors.forename: Adebayo O
authors.initials: AO
authors.lastname: Oyekan
keywords: GLUT4; angiotensin 2; hemodynamics; indinavir; medullary blood flow