Effect of Troglitazone on Blood Pressure, Glut Expression, Glucose Uptake and Reactivity of Vascular Smooth Muscle in Doca/Salt Hypertension.

Abstract

P73 We previously demonstrated that glucose transporter (GLUT4) expression was reduced in aorta and carotid arteries of DOCA/salt hypertensive rats. Although this model of hypertension is not insulin resistant, we hypothesized that the insulin sensitizer, troglitazone (TG), stabilizes GLUT expression possibly through maintenance of the differentiated phenotype. DOCA/salt rats and shams were fed either standard chow or ground chow with TG at the rate of 100 mg/rat/day for 4 weeks post-surgery. While there was no difference in blood pressure between the two sham groups, there was a significant (p≤0.009), decrease in systolic BP in the DOCA/TG (157.2±5.66 mmHg) compared to the DOCA/salt (202.2±10.34 mmHg) treated rats. Immunoblotting of extracts of carotid arteries demonstrated that GLUT4 expression was significantly decreased with DOCA/salt and that this was reversed by TG. Decreased GLUT4 with DOCA/salt is specific to vascular tissue since there was no effect in heart. Both the expression and activity (phospho-specific antibody) of Akt/PKB were increased in DOCA/TG carotid arteries compared to DOCA/salt. There was decreased 2-deoxyglucose (2-DOG) uptake in aorta of DOCA/salt rats and this returned to control level in DOCA/TG aorta. We previously showed that DOCA/salt carotid strips exhibited increased agonist stimulated contractility. 2-DOG increased the contractility of sham strips, but had no further effect on DOCA/salt strips. Contractility of DOCA/TG strips is now being compared to DOCA/salt strips. TG (5μM), IGFI (2ng/mL) or the combined treatment of a human fetal-derived vascular smooth muscle cell line for 48-144h demonstrated an increased glucose transporter expression and a parallel increase in Akt expression. Since Akt/PKB is associated with a differentiated phenotype these combined data suggest that the effect of TG on GLUT levels partially may be mediated via increased Akt expression/activity and may explain the salutary effects of TG on BP.