Maintenance of GLUT 4 expression in smooth muscle prevents hypertension‐induced changes in vascular reactivity

Previous studies have shown that expression of GLUT 4 is decreased in arterial smooth muscle of hypertensive rats and mice and that total body overexpression of GLUT 4 in mice prevents enhanced arterial reactivity in hypertension. To demonstrate that the effect of GLUT 4 overexpression on vascular responses is dependent on vascular smooth muscle GLUT 4 rather than on some systemic effect we developed and tested smooth‐muscle‐specific GLUT 4 transgenic mice ( SMG 4). When made hypertensive with angiotensin II , both wild‐type and SMG 4 mice exhibited similarly increased systolic blood pressure. Responsiveness to phenylephrine, serotonin, and prostaglandin F 2α was significantly increased in endothelium‐intact aortic rings from hypertensive wild‐type mice but not in aortae of SMG 4 mice. Inhibition of Rho‐kinase equally reduced serotonin‐stimulated contractility in aortae of hypertensive wild‐type and SMG 4‐mice. In addition, acetylcholine‐stimulated relaxation was significantly decreased in aortic rings of hypertensive wild‐type mice, but not in rings of SMG 4 mice. Inhibition of either prostacylin receptors or cyclooxygenase‐2 reduced relaxation in rings of hypertensive SMG 4 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 SMG 4 aortae compared to nonhypertensive controls. Our results demonstrate that smooth muscle expression of GLUT 4 exerts a major effect on smooth muscle contractile responses and endothelium‐dependent vasorelaxation and that normal expression of GLUT 4 in vascular smooth muscle is required for appropriate smooth muscle and endothelial responses.