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Renal responses to angiotensin II are attenuated in knockout mice lacking the gene for tumor necrosis factor‐α
Author(s) -
Kopkan Libor,
Castillo Alexander,
Francis Joseph,
Majid Dewan S. A.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a501-d
Subject(s) - endocrinology , medicine , chemistry , renal function , angiotensin ii , excretion , kidney , renal blood flow , blood pressure
To examine the role of tumor necrosis factor‐???TNF‐a) in the renal actions of angiotensin II (ANGII), we assessed the responses to acute ANG II (1 ng/min/g for 30 min, iv) in anesthetized TNF‐a knockout (KO) mice and compared these responses with those of wild type (WT) mice. Renal blood flow (RBF) and glomerular filtration rate (GFR) were measured by PAH and inulin clearances respectively. Compared to WT (n=6), KO (n=8) mice did not have significant differences in the basal values of mean arterial pressure (AP; 92±4 and 99±2 mmHg), 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) and sodium excretion (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 to WT. ANG II caused similar increment in AP in both KO and WT (?24±3 and ?26±2 mmHg). Interestingly, ANG II caused minimal decrease in RBF (−3±2%) in KO compared to WT (−30±5%). Moreover, ANGII increased GFR in KO (7±2%) but not in WT. There were lower UNOxV (92±19% vs. 143±52%; P<0.05) and UISOV (87±8% vs. 116±14%; P<0.05) responses to ANG II in KO compared to WT. These data indicate that TNF‐a involves in the changes in renal hemodynamics as well as nitrosative and oxidative stress mechanisms induced by ANGII.