Distinct Functions of Vascular Endothelial and Smooth Muscle PPARγ in Regulation of Blood Pressure and Vascular Tone

Thiazolidinediones (TZDs) are peroxisome proliferators—activated receptor gamma (PPARγ) activators that exhibit antihypertensive and vasculoprotective effects. Here we describe the use of Tie2Cre/flox and SM22Cre/flox mice, which respectively lacked PPARγ in the endothelium and the smooth muscle, to study vascular function of PPARγ. Rosiglitazone (RGZ) induced a similar blood pressure (BP)—lowering effect in deoxycorticosterone acetate (DOCA) salt—treated PPARγf/f and SM22Cre/flox mice, whereas Tie2Cre/flox mice were completely resistant to this effect. The femoral arteries lacking endothelial PPARγ exhibited increased reactivity to various vasoconstrictors without a significant alteration in acetylcholine-induced relaxation. In sharp contrast, the vasculature lacking smooth muscle PPARγ had blunted sensitivity to α1-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 PPARγ in regulation of vascular tone.