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Angiotensin II decreases NOS3 expression in the thick ascending limb via TNF‐α
Author(s) -
Ramseyer Vanesa Daniela,
Hong Nancy,
Garvin Jeffrey Lawrence
Publication year - 2008
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.22.2_supplement.162
Subject(s) - endocrinology , medicine , nitric oxide synthase , angiotensin ii , tumor necrosis factor alpha , chemistry , basal (medicine) , western blot , renin–angiotensin system , nitric oxide , blood pressure , biochemistry , insulin , gene
Thick ascending limbs (THALs) play an important role in urinary volume and Na excretion, and thus blood pressure. Nitric oxide (NO) produced by NO synthase type 3 (NOS3) inhibits NaCl absorption in this segment. Angiotensin II (Ang) has been reported to either decrease or not change NOS3 expression in the outer medulla. Ang induces release of tumor necrosis factor alpha (TNF‐α) by THALs, and TNF‐α decreases NOS3 expression in several tissues. We hypothesized that Ang decreases NOS3 expression in medullary THALs (mTHALs) via TNF‐α. First, we measured NOS3 expression in primary cultures of mTHALs after treatment with vehicle, Ang or TNF‐α by Western blot. NOS3 expression decreased by 23±9% ( p <0.02; n =6) and 50±5% ( p <0.00001; n =7) by 10 and 100 nM Ang, respectively. Incubation with 1nM TNF‐α decreased NOS3 by 23±3% ( p <0.0002; n =4). To test whether Ang reduces NOS3 expression via TNF‐α, we then used an antibody against TNF‐α. The antibody blocked the Ang‐induced decrease in NOS3 expression by 54±7% ( p <0.02; n =5). Antibody treatment did not change basal NOS3 expression (Δ −12±7%; p =0.15; n =4). We concluded that: 1) Ang decreases NOS3 expression in mTHALs; and 2) the majority of this effect is mediated by TNF‐α. Ang‐induced decreases in mTHAL NOS3 may be one mechanism by which Ang increases Na retention. Research support: HL028982, HL07985.