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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 Wang1, J. David Symons2,3, Hui Zhang1, Zhanjun Jia1, Frank J. Gonzalez4 and Tianxin Yang1

1 Department of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Center, Salt Lake City
2 College of Health, University of Utah, Salt Lake City
3 Division of Endocrinology, Metabolism and Diabetes, University of Utah, Salt Lake City
4 National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Correspondence: Tianxin Yang, MD, PhD, University of Utah and Veterans Affairs Medical Center, Division of Nephrology and Hypertension, 30 N 1900 E, Rm 4R312, Salt Lake City, UT 84132; e-mail:Tianxin.Yang{at}hsc.utah.edu.

Thiazolidinediones (TZDs) are peroxisome proliferators–activated receptor gamma (PPAR{gamma}) activators that exhibit antihypertensive and vasculo-protective 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.

Key Words: PPAR{gamma} • rosiglitazone • endothelial cells • smooth muscle cells • blood pressure

Abbreviations: ACh, acetylcholine • Ang II, angiotensin II • BP, blood pressure • Cre, Cre recombinase • DOCA, deoxycorticosterone acetate • ECs, endothelial cells • L-NMMA, NG monomethyl-L-arginine • MAP, mean arterial pressure • PE, phenylephrine • PPAR{gamma}, peroxisome proliferators–activated receptor gamma • RGZ, rosiglitazone • SM22Cre/flox, mice homozygous for the PPAR{gamma} floxed allele and heterozygous the SM22-Cre transgene (smooth muscle PPAR{gamma} deficient) • SNP, sodium nitroprusside • Tie2Cre/flox, mice homozygous for the PPAR{gamma} floxed allele and heterozygous the Tie2-Cre transgene (endothelial PPAR{gamma} deficient) • TZD, thiazolidinedione • VSMCs, vascular smooth muscle cells

This version was published on January 1, 2009

Toxicologic Pathology, Vol. 37, No. 1, 21-27 (2009)
DOI: 10.1177/0192623308328545
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