Modulation of cardiac and aortic peroxisome proliferator-activated receptor-gamma expression by oxidative stress in chronically glucose-fed rats.

BACKGROUND: The aim of the present study was to examine the chronic effects of alpha-lipoic acid on proliferator peroxisome activated receptors-gamma (PPAR-gamma) and PPAR-alpha expressions in cardiovascular tissues of chronically hypertensive insulinoresistant rats. We have also evaluated the chronic effects of high levels of insulin, glucose, or both on superoxide anion (O(2)(-)) production in aortic smooth muscle cells (SMCs) in the presence or in absence of pioglitazone, a PPAR-gamma agonist.

METHODS: The PPAR-gamma and PPAR-alpha expressions were measured by Western blot. The oxidative stress was evaluated by measuring the O(2)(-) production using the lucigenin method.

RESULTS: Increases in blood pressure, in aortic O(2)(-) production, in glucose or insulin levels, and in insulin resistance, as well as the decrease in PPAR-gamma protein levels in aorta and heart tissues were prevented or attenuated in glucose-treated rats fed with lipoic acid. Chronic treatment with pioglitazone prevented the marked increase in O(2)(-) production in cultured SMCs chronically treated with high insulin combined or not with high glucose levels.

CONCLUSIONS: The combined therapy with the antioxidant alpha-lipoic acid restored PPAR-gamma levels in cardiovascular tissues and attenuated or prevented the development of insulin resistance and hypertension in chronically glucose-fed rats. Moreover, the finding that pioglitazone was also efficient in preventing the increase in oxidative stress in SMCs treated with high insulin combined with high glucose concentrations supports the hypothesis that the activation of PPAR-gamma activity can counteract the oxidative stress that seems to be implicated in the development of hypertension and insulin resistance.