Protective role of the endothelial isoform of nitric oxide synthase in angiotensin II induced inflammatory responses in the kidney.

Protective role of the endothelial isoform of nitric oxide synthase in angiotensin II induced inflammatory responses in the kidney. Am J Physiol Renal Physiol. 2013 Aug 7; Authors: Whiting C, Castillo A, Haque MZ, Majid DS Abstract 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 angiotensin II (AngII) induced hypertension and renal injury by minimizing oxidative stress and the inflammation induced by tumor necrosis factor-alpha (TNF-α). Systemic blood pressure (SBP) and renal injury responses to chronic infusions of AngII (via implanted mini-pumps) were evaluated for 2 weeks in wild type (WT) and in eNOS knockout mice (KO) co-treated 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 i.p.). In study 1, when AngII was given at a dose of 25 ng/min, it increased mean SBP in WT (Δ 36± 3 mmHg; n=7) and this effect was attenuated in mice pretreated with tempol (Δ 24±3 mmHg; n=6). In KO mice (n=9), this dose of AngII 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 AngII (10 ng/min) that increased SBP slightly in WT (Δ 17 ± 7 mmHg; n=6) but exaggeratedly in KO (Δ 48 ± 12 mmHg, n=6) associated with severe renal injury. Co-treatment with either tempo...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research