Peroxisome proliferator-activated receptor-α and receptor-γ activators prevent cardiac fibrosis in mineralocorticoid-dependent hypertension

Iglarz, M., Touyz, R.M. , Viel, E.C., Paradis, P., Amiri, F., Diep, Q.N. and Schiffrin, E.L. (2003) Peroxisome proliferator-activated receptor-α and receptor-γ activators prevent cardiac fibrosis in mineralocorticoid-dependent hypertension. Hypertension, 42(4), pp. 737-743. (doi: 10.1161/01.HYP.0000083511.91817.B1)

Abstract

Peroxisome proliferator-activated receptor (PPAR) activation may prevent cardiac hypertrophy and inhibit production of endothelin-1 (ET-1), a hypertrophic agent. The aim of this in vivo study was to investigate the effects of PPAR activators on cardiac remodeling in DOCA-salt rats, a model overexpressing ET-1. Unilaterally nephrectomized 16-week-old Sprague-Dawley rats (Uni-Nx) were randomly divided into 4 groups: control rats, DOCA-salt, DOCA-salt+rosiglitazone (PPAR-γ activator, 5 mg/kg per day), and DOCA-salt+fenofibrate (PPAR-α activator, 100 mg/kg per day). After 3 weeks of treatment, mean arterial blood pressure was significantly increased in DOCA-salt by 36 mm Hg. Mean arterial blood pressure was normalized by coadministration of rosiglitazone but not by fenofibrate. Both PPAR activators prevented cardiac fibrosis and abrogated the increase in prepro–ET-1 mRNA content in the left ventricle of DOCA-salt rats. Coadministration of rosiglitazone or fenofibrate failed to prevent thickening of left ventricle (LV) walls as measured by echocardiography and the increase in atrial natriuretic peptide mRNA levels. However, rosiglitazone and fenofibrate prevented the decrease in LV internal diameter and thus concentric remodeling of the LV found in DOCA-salt rats. Taken together, these data indicate a modulatory role of PPAR activators on cardiac remodeling in mineralocorticoid-induced hypertension, in part associated with decreased ET-1 production.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Touyz, Professor Rhian
• Authors: Iglarz, M., Touyz, R.M., Viel, E.C., Paradis, P., Amiri, F., Diep, Q.N., and Schiffrin, E.L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Hypertension
• ISSN: 0194-911X
• ISSN (Online): 1524-4563
• Published Online: 14 July 2003