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.
Wang
Ningning
N
Department of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Center, Salt Lake City, UT 84132, USA.
Symons
J David
JD
Zhang
Hui
H
Jia
Zhanjun
Z
Gonzalez
Frank J
FJ
Yang
Tianxin
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D003900:Desoxycorticosterone / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D005263:Femoral Artery / Q000187:drug effects / Q000503:physiopathology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D047495:PPAR gamma / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D047495:PPAR gamma; D045162:Thiazolidinediones; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000077154:Rosiglitazone; D003900:Desoxycorticosterone