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Connecting tubule glomerular feedback (CTGF) antagonizes tubuloglomerular feedback (TGF) in vivo
Author(s) -
Wang Hong,
Garvin Jeffrey L.,
Carretero Oscar A.
Publication year - 2010
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.24.1_supplement.lb699
Subject(s) - ctgf , tubuloglomerular feedback , endocrinology , medicine , chemistry , transforming growth factor , proximal tubule , kidney , growth factor , receptor
We recently described that there is crosstalk between the connecting tubule (CNT) and the Af‐Art that causes dilation. CTGF is mediated by CNT Na transport via epithelial Na channels (ENaC). We hypothesized that CTGF opposes TGF. We performed renal micropuncture studies in male rats. We induced TGF by increasing late proximal perfusion rate (0, 10, 20, 40, 80 nL/min). Stop‐flow pressure (P SF ) was used as an index of TGF response. First, we showed that TGF was reversible and reproducible. Next, we tested whether inhibition of CTGF with benzamil (ENaC inhibitor; 1 μM) potentiated TGF. In control, high flow (80 nL/min) increased P SF indicating that CTGF increased Af‐Art dilatation. CTGF inhibition with benzamil potentiated the TGF response, especially at high flow rates. When NaCl transport in the distal tubule was inhibited with hydrochlorothiazide (HCTZ, 1 mM) to increase delivery of Na to the CNT, benzamil potentiated the TGF response at lower (20 nL/min) flow rates ( Table). We conclude that CTGF antagonizes the vasoconstrictor effect of TGF.Perfusion rate (nL/min) 0 10 20 40 80Control P SF (n=5) 39.6 ± 0.8 39.2 ± 0.6 36.4 ± 0.8 32.4 ± 0.9 34.2 ± 0.8 † Benzamil P SF 39.1 ± 0.8 38.7 ± 0.7 35.7 ± 0.9 30.1 ± 0.8 ** 30.1 ± 0.7 *** HCTZ P SF (n=4) 40.0 ± 0.6 40.3 ± 0.6 37.4 ± 0.5 33.5 ± 0.8 35.5 ± 0.8 † HCTZ+Benzamil P SF 39.8 ± 0.4 39.9 ± 0.5 35.8 ± 0.4 # 31.0 ± 0.6 # 30.9 ± 0.6 #** p < 0.01 and*** p < 0.001 vs. control;# p < 0.05 vs. HCTZ;† p < 0.001 40 vs. 80 nL/minSource of Funding: This study was supported by NIH Grants HL028982 and HL088036.