Distinct functions of vascular endothelial and smooth muscle PPARgamma in regulation of blood pressure and vascular tone.

Thiazolidinediones (TZDs) are peroxisome proliferators-activated receptor gamma (PPARgamma) activators that exhibit antihypertensive and vasculo-protective effects. Here we describe the use of Tie2Cre/flox and SM22Cre/flox mice, which respectively lacked PPARgamma in the endothelium and the smooth muscle, to study vascular function of PPARgamma. Rosiglitazone (RGZ) induced a similar blood pressure (BP)-lowering effect in deoxycorticosterone acetate (DOCA) salt-treated PPARgamma(f/f) and SM22Cre/flox mice, whereas Tie2Cre/flox mice were completely resistant to this effect. The femoral arteries lacking endothelial PPARgamma exhibited increased reactivity to various vasoconstrictors without a significant alteration in acetylcholine-induced relaxation. In sharp contrast, the vasculature lacking smooth muscle PPARgamma had blunted sensitivity to alpha1-adrenergic agents but enhanced sensitivity to acetylcholine. Our results demonstrated endothelium but not smooth muscle as the site for TZD-induced BP-lowering effect and also uncovered distinct functions of endothelial and smooth muscle PPARgamma in regulation of vascular tone.