Pioglitazone improves endothelial function in a dose‐dependent manner in rats with hypercholesterolemia

Objective It has been confirmed that hypercholesterolemia cause endothelial cell (EC) dysfunction, which is a prerequisite of atherosclerosis. Peroxisome proliferator‐activated receptors (PPARs) activation has been reported to attenuate the formation of atherosclerosis. This study was designed to investigate the effects of pioglitazone, a PPARγ agonist, on endothelial cell (EC) dysfunction in hypercholesterolemic rats. Methods Male Wistar rats were assigned to one of the following groups: control (C, normal diet); hypercholesterolemia (HC, high‐cholesterol diet for 8 weeks); and HC treated with pioglitazone (respectively 1.5,3,10,20mg/kg/day for the last 4 weeks). EC function was determined by comparing vasorelaxation to Ach, an EC‐dependent, and acidified NaNO2, an EC‐independent vasodilator. Data was analyzed with ANOVA. Results HC caused a significant EC dysfunction (maximal relaxation to Ach: 50.51±2.45% vs. 99.73±3.04% in C, P<0.01). Treatment with pioglitazone improved EC function in a dose‐dependent manner, and the dose of 10 mg/kg/day is the best (maximal relaxation to Ach: 97.86±3.35% vs. HC, P<0.01). There was no difference in vasorelaxation to acidified NaNO2 among the groups. Conclusion Our study demonstrates that in vivo treatment with a PPARγ agonist can improve EC function.