| First Author | Chang L | Year | 2009 |
| Journal | Circulation | Volume | 119 |
| Issue | 16 | Pages | 2161-9 |
| PubMed ID | 19364979 | Mgi Jnum | J:166495 |
| Mgi Id | MGI:4845839 | Doi | 10.1161/CIRCULATIONAHA.108.815803 |
| Citation | Chang L, et al. (2009) Vascular smooth muscle cell-selective peroxisome proliferator-activated receptor-gamma deletion leads to hypotension. Circulation 119(16):2161-9 |
| abstractText | BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists are commonly used to treat diabetes, although their PPARgamma-dependent effects transcend their role as insulin sensitizers. Thiazolidinediones lower blood pressure (BP) in diabetic patients, whereas results from conventional/tissue-specific PPARgamma experimental models suggest an important pleiotropic role for PPARgamma in BP control. Little evidence is available on the molecular mechanisms underlying the role of vascular smooth muscle cell-specific PPARgamma in basal vascular tone. METHODS AND RESULTS: We show that vascular smooth muscle cell-selective deletion of PPARgamma impairs vasoactivity with an overall reduction in BP. Aortic contraction in response to norepinephrine is reduced and vasorelaxation is enhanced in response to beta-adrenergic receptor (beta-AdR) agonists in vitro. Similarly, vascular smooth muscle cell-selective PPARgamma knockout mice display a biphasic response to norepinephrine in BP, reversible on administration of beta-AdR blocker, and enhanced BP reduction on treatment with beta-AdR agonists. Consistent with enhanced beta2-AdR responsiveness, we found that the absence of PPARgamma in vascular smooth muscle cells increased beta2-AdR expression, possibly leading to the hypotensive phenotype during the rest phase. CONCLUSIONS: These data uncovered the beta2-AdR as a novel target of PPARgamma transcriptional repression in vascular smooth muscle cells and indicate that PPARgamma regulation of beta2-adrenergic signaling is important in the modulation of BP. |
