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354 RENAL RESPONSES TO ANGIOTENSIN II IN MICE LACKING THE GENE FOR TUMOR NECROSIS FACTOR-α.
  1. L. Kopkan1,
  2. A. Castillo1,
  3. J. Francis2,
  4. D. S.A. Majid1
  1. 1Department of Physiology, Tulane University Health Sciences Center, Hypertension and Renal Center of Excellence, New Orleans, LA
  2. 2Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, LA

Abstract

Recent studies have implicated a role for a proinflammatory cytokine, tumor necrosis factor-α (TNF-α), in angiotensin II (ANGII)-induced renal injury and the development of salt-sensitive hypertension. To examine this relationship between TNF-α and ANGII actions in the kidney, we assessed renal responses to acute ANG II (1 ng/min/g for 30 minutes, IV) in anesthetized knockout (KO) mice lacking TNF-α and compared these responses with those of wild-type (WT) mice. Systemic blood pressure (BP) was recorded from a cannula placed in the left carotid artery. Renal blood flow (RBF) and glomerular filtration rate (GFR) were measured by PAH and inulin clearances, respectively. Compared with WT (n = 6), KO (n = 8) mice did not have significant differences in the basal values of BP (92 ± 4 and 99 ± 2 mm Hg), RBF (3.8 ± 0.3 and 3.4 ± 0.2 mL.min−1.g−1), GFR (0.74 ± 0.04 and 0.75 ± 0.03 mL.min−1.g−1), urine flow (V, 8.8 ± 0.4 and 9.9 ± 0.6 μL.min−1.g−1), and sodium excretion (UNaV, 0.87 ± 0.07 and 0.93 ± 0.12 μmol.min−1.g−1). However, KO exhibit lower urinary nitrite/nitrate (UNOxV; 0.13 ± 0.02 vs 0.35 ± 0.07 nmol.min−1.g−1) and 8-isoprostane excretion (UISOV; 1.26 ± 0.05 vs 1.97 ± 0.20 pg.min−1.g−1) compared with WT. ANGII caused similar increment in BP in both KO and WT (Δ24 ± 3 and Δ26 ± 2 mm Hg). Interestingly, ANGII caused minimal decrease in RBF (−3 ± 2%) in KO compared with WT (−30 ± 5%). Moreover, ANGII increased GFR in KO (7 [138} 2%) but not in WT. Although V and UNaV responses to ANGII were not much different between the the strains, there were lower UNOxV (92 ± 19% vs 143 [138} 52%; p < .05) as well as UISOV (87 ± 8% vs 116 ± 14%; p < .05) responses to ANGII in KO compared with WT mice. These data indicate that TNF-α is involved in the changes in renal hemodynamics as well as nitrosative and oxidative stress mechanisms induced by ANGII.

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