Protective role of the endothelial isoform of nitric oxide synthase in ANG II-induced inflammatory responses in the kidney
| Autor: | Dewan S. A. Majid, Mohammed Z. Haque, Curtis Whiting, Alexander Castillo |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Male
Gene isoform medicine.medical_specialty Nitric Oxide Synthase Type III Physiology Nitric Oxide Endothelial no synthase Nitric oxide Mice chemistry.chemical_compound Enos Internal medicine medicine Animals Inflammation Mice Knockout Kidney Nephritis biology Superoxide Angiotensin II Ribonuclease Pancreatic Articles biology.organism_classification Up-Regulation Nitric oxide synthase Oxidative Stress medicine.anatomical_structure Endocrinology chemistry Hypertension biology.protein Angiogenesis Inducing Agents |
| Zdroj: | American Journal of Physiology-Renal Physiology. 305:F1031-F1041 |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.00024.2013 |
| Popis: | 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-α. 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-α 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 (Δ36 ± 3 mmHg; n = 7), and this effect was attenuated in mice pretreated with tempol (Δ24 ± 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 (Δ17 ± 7 mmHg; n = 6) but exaggeratedly in KO (Δ48 ± 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. |
| Databáze: | OpenAIRE |
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