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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Inhibitory effects of PPAR-gamma on endothelin-1-induced inflammatory pathways in vascular smooth muscle cells from normotensive and hypertensive rats

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Author(s):
Montezano, Augusto C. [1] ; Amiri, Farhad [2] ; Tostes, Rita C. [1] ; Touyz, Rhian M. [3] ; Schiffrin, Ernesto L. [2]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil
[2] Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Hypertens & Vasc Res Unit, Montreal, PQ H3T 1E2 - Canada
[3] Univ Ottawa, Ottawa Hlth Res Inst, Kidney Res Ctr, Ottawa, ON - Canada
Total Affiliations: 3
Document type: Journal article
Source: JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION; v. 1, n. 2, p. 150-160, MAR-APR 2007.
Web of Science Citations: 15
Abstract

The present study evaluated the effects of endothelin (ET)-1 and the peroxisome proliferator activated receptor gamma (PPAR-gamma) agonist, rosiglitazone, on inflammatory markers in vascular smooth muscle cells (VSMCs) from normotensive (WKY) and hypertensive (SHRSP) rats. Rat VSMC-derived mesenteric arteries from WKY and SHRSP were treated with ET-1 (100 mmol/L) and rosiglitazone (1 mu mol/L) or ET type A (ET(A)) or type B (ET(B)) receptor antagonists. Nuclear factor kappa-B (NF kappa B) binding activity was assessed by electrophoretic mobility shift assay and phospho-inhibitory kappa B (I kappa B); vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, and cyclooxygenase (COX)-2 expression was determined using Western blotting. ET-1 significantly increased NF kappa B binding, and VCAM-1, ICAM, and COX-2 expression to a greater degree in SHRSP than in WKY VSMC. These changes were associated with increased phosphorylation of I kappa B, thus resulting in decreased NF kappa B inhibition. Co-incubation with PPAR-gamma activator rosiglitazone, or ET(A) or ET(B) receptor antagonism prevented ET-1-stimulated vascular proinflammatory effects in both WKY and SHRSP VSMC. Proinflammatory effects of ET-1 in VSMCs are mediated via both ET(A) and ET(B) receptor subtypes. These effects may be abrogated by the PPAR-gamma activator rosiglitazone. PPAR-gamma activators may thus prevent deleterious ET-1-dependent proinflammatory vascular effects in VSMC in hypertension. (C) 2007 American Society of Hypertension. All rights reserved. (AU)