| First Author | Santhanam AV | Year | 2012 |
| Journal | Brain Res | Volume | 1483 |
| Pages | 89-95 | PubMed ID | 22982594 |
| Mgi Jnum | J:193576 | Mgi Id | MGI:5468781 |
| Doi | 10.1016/j.brainres.2012.09.012 | Citation | Santhanam AV, et al. (2012) PPARdelta agonist GW501516 prevents uncoupling of endothelial nitric oxide synthase in cerebral microvessels of hph-1 mice. Brain Res 1483:89-95 |
| abstractText | Peroxisome proliferator-activated receptor delta (PPARdelta) is ubiquitously expressed in the vasculature, including cerebral circulation. The role of PPARdelta in metabolism of tetrahydrobiopterin (BH(4)) has not been studied in the cerebral microvasculature. In the present study, the effects of PPARdelta agonist GW501516 on uncoupling of endothelial nitric oxide synthase (eNOS) were determined in cerebral microvessels of BH(4)-deficient hph-1 mice. Wild-type (B6CBA) and hph-1 mice were orally gavaged with a selective PPARdelta activator, GW501516 (2 mg/kg/day) for 14 days, and thereafter, cerebral microvessels were isolated and studied. Treatment of hph-1 mice with GW501516 significantly reduced oxidation of BH(4) and increased the ratio of BH(4) to 7,8-BH(2) (P<0.05, n=6-9). Attenuation of L-NAME-inhibitable superoxide anion levels by GW501516 demonstrated that activation of PPARdelta might prevent uncoupling of endothelial nitric oxide synthase (eNOS, P<0.05, n=6-9). Western blotting studies demonstrated that GW501516 selectively increased the endothelial expressions of CuZn superoxide dismutase (P<0.05, n=6-9) and catalase (P<0.05, n=6-8). PPARdelta activation increased the total nitrite and nitrate (NO(2)+NO(3)) content in cerebral microvessels (P<0.05, n=6). Obtained results suggest that in vivo activation of PPARdelta prevents eNOS uncoupling, restores bioavailability of NO and may help preserve endothelial function in the BH(4)-deficient cerebral circulation. |
