Effect of Peroxisome Proliferator–Activated Receptor-α and -γ Activators on Vascular Remodeling in Endothelin-Dependent Hypertension

Abstract
Objective— Peroxisome proliferator–activated receptors (PPARs) may modulate in vitro the vascular production of vasoactive peptides such as endothelin-1 (ET-1). Thus, we investigated in vivo the interaction between PPARs and ET-1 in deoxycorticosterone acetate (DOCA)–salt rats that overexpress vascular ET-1. Methods and Results— Unilaterally nephrectomized 16-week-old Sprague-Dawley rats (Uni-Nx) were divided into 4 groups (n=6 each): control group, DOCA-salt group, DOCA-salt+PPAR-γ activator (rosiglitazone, 5 mg · kg−1 · d−1), or DOCA-salt+PPAR-α activator (fenofibrate, 100 mg · kg−1 · d−1). Systolic blood pressure was significantly increased in the DOCA-salt group (240±11 vs 121±2 mm Hg in Uni-Nx, PPPConclusions— PPAR-α and -γ activators were able to modulate endogenous production of ET-1 and had beneficial vascular effects in endothelin-dependent hypertension.

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