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Toxicologic Pathology
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Article

Distinct Functions of Vascular Endothelial and Smooth Muscle PPAR{gamma} in Regulation of Blood Pressure and Vascular Tone

Ningning Wang, J. David Symons, Hui Zhang, Zhanjun Jia, Frank J. Gonzalez, and Tianxin Yang*

* To whom correspondence should be addressed. E-mail: Tianxin.Yang{at}hsc.utah.edu.


  Abstract
Thiazolidinediones (TZDs) are peroxisome proliferators–activated receptor gamma (PPAR{gamma}) activators that exhibit antihypertensive and vasculoprotective effects. Here we describe the use of Tie2Cre/flox and SM22Cre/flox mice, which respectively lacked PPAR{gamma} in the endothelium and the smooth muscle, to study vascular function of PPAR{gamma}. Rosiglitazone (RGZ) induced a similar blood pressure (BP)–lowering effect in deoxycorticosterone acetate (DOCA) salt–treated PPAR{gamma}f/f and SM22Cre/flox mice, whereas Tie2Cre/flox mice were completely resistant to this effect. The femoral arteries lacking endothelial PPAR{gamma} exhibited increased reactivity to various vasoconstrictors without a significant alteration in acetylcholine-induced relaxation. In sharp contrast, the vasculature lacking smooth muscle PPAR{gamma} had blunted sensitivity to {alpha}1-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 PPAR{gamma} in regulation of vascular tone.

First published on December 15, 2008, doi:10.1177/0192623308328545

Toxicologic Pathology 2009;37:21.

A more recent version of this article appeared on January 1, 2009

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