on May 12, 2005
Published online before print May 12, 2005, doi: 10.1161/01.ATV.0000170137.41079.ab
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Submitted on August 31, 2004
Accepted on May 2, 2005
GLUT4 Facilitative Glucose Transporter Specifically and Differentially Contributes to Agonist-Induced Vascular Reactivity in Mouse Aorta
James L. Park ;
From the Departments of Internal Medicine (J.L.P., R.D.L., D.D., H.Z., B.KD., J.C., K.B.A., M.S., A.K.K., F.C.B.) and Physiology (R.D.L., F.C.B.), University of Michigan Medical School, Ann Arbor, Mich; the Department of Biochemistry (M.J.C.), Albert Einstein College of Medicine; and the Hypertension and Vascular Research Division (N.A., P.J.P.), Henry Ford Hospital.
* To whom correspondence should be addressed. E-mail: fbrosius{at}umich.edu.
Objective--We hypothesized that GLUT4 is a predominant facilitative glucose transporter in vascular smooth muscle cells (VSMCs), and GLUT4 is necessary for agonist-induced VSMC contraction.
Methods and Results--Glucose deprivation and indinavir, a GLUT4 antagonist, were used to assess the role of GLUT4 and non-GLUT4 transporters in vascular reactivity. In isolated endothelium-denuded mouse aorta, 
50% of basal glucose uptake was GLUT4-dependent. Norepinephrine-mediated contractions were dependent on both GLUT4 and non-GLUT4 transporters, serotonin (5-HT)-mediated contractions were mainly GLUT4-dependent, and prostaglandin (PG) F2
-mediated contractions were dependent on non-GLUT4 transporters, whereas indinavir had no effect in GLUT4 knockout vessels. We also observed a 46% decrease in GLUT4 expression in aortas from angiotensin II hypertensive mice. Indinavir caused a less profound attenuation of maximal 5-HT-mediated contraction in these vessels, corresponding to the lower GLUT4 levels in the hypertensive aortas. Finally, and somewhat surprisingly, chronic GLUT4 knockout was associated with increased vascular reactivity compared with that in wild-type animals, suggesting that chronic absence or reduction of GLUT4 expression in VSMCs leads to opposite effects observed with acute inhibition of GLUT4.
Conclusions--Thus, we conclude that GLUT4 is constitutively expressed in large arteries and likely participates in basal glucose uptake. In addition, GLUT4, as well as other non-GLUT4 facilitative glucose transporters, are necessary for agonist-induced contraction, but each transporter participates in VSMC contraction selectively, depending on the agonist, and changes in GLUT4 expression may account for some of the functional changes associated with vascular diseases like hypertension.
Key words: glucose • GLUT4 • indinavir • vascular smooth muscle
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