Abstract 5563: Pioglitazone Improves Endothelium-Dependent Vasodilation in Hypertensive Patients With Impaired Glucose Tolerance Through a Decrease in Oxidative Stress
Objective: The aim of this study was to determine long-term pioglitazone treatment restores endothelial function in hypertensive patients with impaired glucose tolerance (IGT) and to elucidate the roles of oxidative stress and insulin resistance in endothelial function/
Research Design and Methods: We evaluated the effects of pioglitazone treatment for 12 weeks on forearm blood flow (FBF) responses to acetylcholine (Ach), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator, in 34 hypertensive patients with IGT who were randomly divided into a pioglitazone group (n=17) and a conventional therapygroup (control group) (n=17) and in 34 age- and gender-matched healthy subjects. FBF was measured by using a strain-gauge plethysmography.
Results: FBF response to ACh was greater in healthy subjects than in hypertensive patients with IGT, although the FBF responses to SNP were similar in the two groups. Pioglitazone increased the FBF responses to ACh from 16.3±6.8 to 23.6±7.1 mL/min per 100 mL tissue (P<0.05) and decreased urinary excretion of 8-hydroxy-2′-deoxyguanosine, an indez of oxidative stress. Pioglitazone did not alter SNP-stimulated vasodilation. Administration of NG-monomethyl-L-arginine, a nitric oxide (NO) synthase inhibitor, abolished the augmentation of FBF responses to ACh correlated with the decrease in urinary extretion of 8-hydroxy-2′-deoxyguanosine but not with changes in other parameters (r=−0.36, P<0.01).
Conclusion: These findings suggest that pioglitazone improves endothelial function in hypertensive patients with IGT through an increase in NO bioavailability by, at least in part, a decrease in oxidative stress.