title: GLUT4 facilitative glucose transporter specifically and differentially contributes to agonist-induced vascular reactivity in mouse aorta.
abstract: 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.
  
  
  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, approximately 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) F(2alpha)-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.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Park
authors.forename: Robert D
authors.initials: RD
authors.lastname: Loberg
authors.forename: Damon
authors.initials: D
authors.lastname: Duquaine
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhang
authors.forename: Baljit K
authors.initials: BK
authors.lastname: Deo
authors.forename: Noelia
authors.initials: N
authors.lastname: Ardanaz
authors.forename: Jami
authors.initials: J
authors.lastname: Coyle
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Atkins
authors.forename: MaryLee
authors.initials: M
authors.lastname: Schin
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: Charron
authors.forename: Arno K
authors.initials: AK
authors.lastname: Kumagai
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Pagano
authors.forename: Frank C
authors.initials: FC
authors.lastname: Brosius
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D015237:Dinoprost / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D019469:Indinavir / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D017320:HIV Protease Inhibitors; C495678:Slc2a1 protein, mouse; C495693:Slc2a4 protein, mouse; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D012701:Serotonin; D019469:Indinavir; D015237:Dinoprost; D005947:Glucose; D009638:Norepinephrine