Montezano Augusto C, Amiri Farhad, Tostes Rita C, Touyz Rhian M, Schiffrin Ernesto L
Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
J Am Soc Hypertens. 2007 Mar-Apr;1(2):150-60. doi: 10.1016/j.jash.2007.01.005.
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 (1mumol/L) or ET type A (ET(A)) or type B (ET(B)) receptor antagonists. Nuclear factor kappa-B (NFkappaB) binding activity was assessed by electrophoretic mobility shift assay and phospho-inhibitory kappaB (IkappaB); 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 NFkappaB 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 IkappaB, thus resulting in decreased NFkappaB 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.
