Abstract
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 (PSF) 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 PSF 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 80 Control PSF (n=5) 39.6 ± 0.8 39.2 ± 0.6 36.4 ± 0.8 32.4 ± 0.9 34.2 ± 0.8† Benzamil PSF 39.1 ± 0.8 38.7 ± 0.7 35.7 ± 0.9 30.1 ± 0.8** 30.1 ± 0.7*** HCTZ PSF (n=4) 40.0 ± 0.6 40.3 ± 0.6 37.4 ± 0.5 33.5 ± 0.8 35.5 ± 0.8† HCTZ+Benzamil PSF 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/min Source of Funding: This study was supported by NIH Grants HL028982 and HL088036.
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