Abstract
Objective: Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor gamma (PPARγ) ligand, has been reported to function like an insulin sensitizer and exerts cardiovascular actions. The activation of PPARγ has been described to have antiapoptotic effects in renal ischemia-reperfusion models. We hypothesized that RGZ exerts a PPARγ–dependent regulation of blood pressure and decreases kidney apoptosis in an experimental model of hypertension. Design and method: We performed the experiments in normotensive (sham) and aortic coarctation (AoCo)-induced hypertensive male Wistar rats. Both sham- and AoCo rats were treated for 7 days with vehicle (V), RGZ (5 mg/kg/day) or RGZ plus BADGE (120 mg/kg/day). After treatment, we measured blood pressure and vascular reactivity on aortic rings as well as the expression and activity of renin-angiotensin system (RAS) components. To study the effect on renal apoptosis, we isolated the kidneys, separated both, cortex and medulla, and evaluated the expression of apoptotic (Bax) and anti-apoptotic proteins (14-3-3ε, p-Akt and Bcl2) in both regions. Results: RGZ in AoCo group decreased blood pressure values and improved vascular response to ACh in a PPAR dependent manner. RGZ lowered serum AngII- but increased Ang-(1–7) levels. Also, RGZ decreased oxidative stress markers and improved antioxidant capacity. Regarding protein expression of ACE and AT1, it was lower in RGZ- than in vehicle-treated rats but the expression of ACE2, MAS, and AT2 receptors was increased. Regarding renal apoptosis, in the cortex from AoCo-ischemic kidney Bax was increased, while 14-3-3ε and PPARγ proteins were decreased. Treatement with RGZ, prevented PPARγ and 14-3-3ε lower expression, however, it had no effect on Bax expression. With respect Bcl-2 expression was slightly increased in RGZ-treated group. These effects were not observed in medulla were proteins evaluated presented no differences in expression in all four groups. Conclusions: We conclude that RGZ lowers blood pressure values by reducing the expression of ACE, decreasing the levels of AngII, and increasing levels of Ang-(1–7) in a PPARγ-dependent manner. RGZ decreases apoptosis in renal cortex and medulla in hypertensive rats. The increase of PPARγ, Bcl-2 and 14-3-3ε observed in renal cortex could contribute to this effect.
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