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.
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