| First Author | Whiting C | Year | 2013 |
| Journal | Am J Physiol Renal Physiol | Volume | 305 |
| Issue | 7 | Pages | F1031-41 |
| PubMed ID | 23926180 | Mgi Jnum | J:202044 |
| Mgi Id | MGI:5516535 | Doi | 10.1152/ajprenal.00024.2013 |
| Citation | Whiting C, et al. (2013) Protective role of the endothelial isoform of nitric oxide synthase in ANG II-induced inflammatory responses in the kidney. Am J Physiol Renal Physiol 305(7):F1031-41 |
| abstractText | In the present study, we examine the hypothesis that the nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays a protective role in the development of ANG II-induced hypertension and renal injury by minimizing oxidative stress and the inflammation induced by TNF-alpha. Systolic blood pressure (SBP) and renal injury responses to chronic infusions of ANG II (via implanted minipumps) were evaluated for 2 wk in wild-type (WT) and in eNOS knockout mice (KO) cotreated with or without a superoxide (O2(-)) scavenger, tempol (400 mg/l in the drinking water), or a TNF-alpha receptor blocker, etanercept (5 mg/kg/day ip). In study 1, when ANG II was given at a dose of 25 ng/min, it increased mean SBP in WT mice (Delta36 +/- 3 mmHg; n = 7), and this effect was attenuated in mice pretreated with tempol (Delta24 +/- 3 mmHg; n = 6). In KO mice (n = 9), this dose of ANG II resulted in severe renal injury associated with high mortality. To avoid this high mortality in KO, study 2 was conducted with a lower dose of ANG II (10 ng/min) that increased SBP slightly in WT (Delta17 +/- 7 mmHg; n = 6) but exaggeratedly in KO (Delta48 +/- 12 mmHg, n = 6) associated with severe renal injury. Cotreatment with either tempol (n = 6) or etanercept (n = 6) ameliorated the hypertensive, as well as the renal injury responses in KO compared with WT. These data demonstrate a protective role for eNOS activity in preventing renal inflammatory injury and hypertension induced by chronic increases in ANG II. |
