Effect of peroxisome proliferator-activated receptor-α and -γ activators on vascular remodeling in endothelin-dependent hypertension

Iglarz, M., Touyz, R.M. , Amiri, F., Lavoie, M.F., Diep, Q.N. and Schriffin, E.L. (2003) Effect of peroxisome proliferator-activated receptor-α and -γ activators on vascular remodeling in endothelin-dependent hypertension. Arteriosclerosis, Thrombosis, and Vascular Biology, 23(1), pp. 45-51. (doi: 10.1161/01.ATV.0000047447.67827.CD)

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Abstract

<b>Objective—</b> 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.<p></p> <b>Methods and Results—</b> 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, P<0.01). Progression of hypertension was partially prevented by coadministration of rosiglitazone (172±3 mm Hg vs DOCA-salt, P<0.05) but not by fenofibrate. Both PPAR activators abrogated the increase in prepro-ET-1 mRNA content in the mesenteric vasculature of DOCA-salt rats. The media-to-lumen ratio was increased in DOCA-salt rats (10.3±0.9% vs 4.9±0.5% in Uni-Nx rats, P<0.01). Rosiglitazone and fenofibrate prevented the hypertrophic remodeling observed in DOCA-salt rats without affecting vascular stiffness. Rosiglitazone but not fenofibrate prevented endothelial dysfunction in pressurized mesenteric arteries. Finally, both rosiglitazone and fenofibrate prevented the vascular increase in superoxide anion production induced in DOCA-salt animals.<p></p> <b>Conclusions—</b> PPAR-α and -γ activators were able to modulate endogenous production of ET-1 and had beneficial vascular effects in endothelin-dependent hypertension.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Touyz, Professor Rhian
Authors: Iglarz, M., Touyz, R.M., Amiri, F., Lavoie, M.F., Diep, Q.N., and Schriffin, E.L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher:American Heart Association
ISSN:1079-5642
ISSN (Online):1524-4636
Published Online:14 November 2002

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