Maintenance of GLUT4 expression in smooth muscle prevents hypertension-induced changes in vascular reactivity

Kevin B. Atkins, Yoshinori Seki, Jharna Saha, Felix Eichinger, Maureen J. Charron, Frank C. Brosius

Research output: Contribution to journalArticle

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Abstract

Previous studies have shown that expression of GLUT4 is decreased in arterial smooth muscle of hypertensive rats and mice and that total body overexpression of GLUT4 in mice prevents enhanced arterial reactivity in hypertension. To demonstrate that the effect of GLUT4 overexpression on vascular responses is dependent on vascular smooth muscle GLUT4 rather than on some systemic effect we developed and tested smooth-muscle-specific GLUT4 transgenic mice (SMG4). When made hypertensive with angiotensin II, both wild-type and SMG4 mice exhibited similarly increased systolic blood pressure. Responsiveness to phenylephrine, serotonin, and prostaglandin Fwas significantly increased in endothelium-intact aortic rings from hypertensive wild-type mice but not in aortae of SMG4 mice. Inhibition of Rho-kinase equally reduced serotonin-stimulated contractility in aortae of hypertensive wild-type and SMG4-mice. In addition, acetylcholine-stimulated relaxation was significantly decreased in aortic rings of hypertensive wild-type mice, but not in rings of SMG4 mice. Inhibition of either prostacylin receptors or cyclooxygenase-2 reduced relaxation in rings of hypertensive SMG4 mice. Inhibition of cyclooxygenase-2 had no effect on relaxation in rings of hypertensive wild-type mice. Cyclooxygenase-2 protein expression was decreased in hypertensive wild-type aortae but not in hypertensive SMG4 aortae compared to nonhypertensive controls. Our results demonstrate that smooth muscle expression of GLUT4 exerts a major effect on smooth muscle contractile responses and endothelium-dependent vasorelaxation and that normal expression of GLUT4 in vascular smooth muscle is required for appropriate smooth muscle and endothelial responses.

Original languageEnglish (US)
Article numbere12299
JournalPhysiological Reports
Volume3
Issue number2
DOIs
StatePublished - 2015

Fingerprint

Smooth Muscle
Blood Vessels
Maintenance
Hypertension
Transgenic Mice
Aorta
Cyclooxygenase 2
Vascular Smooth Muscle
Endothelium
Serotonin
Blood Pressure
rho-Associated Kinases
Phenylephrine
Vasodilation
Angiotensin II
Acetylcholine
Prostaglandins

Keywords

  • Contractility
  • COX-2
  • Endothelial-dysfunction
  • GLUT4
  • IP-receptors
  • Relaxation

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology

Cite this

Maintenance of GLUT4 expression in smooth muscle prevents hypertension-induced changes in vascular reactivity. / Atkins, Kevin B.; Seki, Yoshinori; Saha, Jharna; Eichinger, Felix; Charron, Maureen J.; Brosius, Frank C.

In: Physiological Reports, Vol. 3, No. 2, e12299, 2015.

Research output: Contribution to journalArticle

Atkins, Kevin B. ; Seki, Yoshinori ; Saha, Jharna ; Eichinger, Felix ; Charron, Maureen J. ; Brosius, Frank C. / Maintenance of GLUT4 expression in smooth muscle prevents hypertension-induced changes in vascular reactivity. In: Physiological Reports. 2015 ; Vol. 3, No. 2.
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