Connecting tubule glomerular feedback mediates tubuloglomerular feedback resetting post-unilateral nephrectomy.

Unilaterally nephrectomized rats (UNx) have higher glomerular capillary pressure (PGC) that can cause significant glomerular injury in the remnant kidney. PGC is controlled by the ratio of afferent (Af-Art) and efferent arteriole resistance. Af-Art resistance in turn is regulated by two intrinsic feedback mechanisms: 1) Tubuloglomerular feedback (TGF) that causes Af-Art constriction in response to increased NaCl in the macula densa and 2) connecting tubule glomerular feedback (CTGF) that causes Af-Art dilatation in response to an increase in NaCl transport in the connecting tubule via the epithelial sodium channel (ENaC). Resetting of TGF post-UNx can allow systemic pressure to be transmitted to the glomerulus and cause renal damage, but the mechanism behind this resetting is unclear. Since CTGF is an Af-Art dilatory mechanism, we hypothesized that CTGF is increased after UNx, and contributes to TGF resetting. To test this hypothesis, we performed UNx in Sprague Dawley (SD) rats. Twenty-four hours after surgery, we performed micropuncture of individual nephrons and measured stop-flow pressure (PSF). PSF is an indirect measurement of PGC. Maximal TGF response at 40nl/min was 8.9 ± 1.24 mmHg in sham-UNx rats and 1.39 ± 1.02 mmHg in UNx rats indicating TGF resetting after UNx. When CTGF was inhibited with the ENaC blocker Benzamil (1μM/L), the TGF response was 12.29 ± 2.01 mmHg in UNx rats and 13.03 ± 1.25 mmHg in sham-UNx rats, indicating restoration of the TGF responses in UNx. We conclude that enhanced CTGF contributes to TGF resetting after UNx. Copyright © 2016, American Journal of Physiology-Renal Physiology.

Citation

Sumit R Monu, Yilin Ren, J X Masjoan Juncos, Kristopher Kutskill, Hong Wang, Nitin Kumar, Edward L Peterson, Oscar A Carretero. Connecting tubule glomerular feedback mediates tubuloglomerular feedback resetting post-unilateral nephrectomy. American journal of physiology. Renal physiology. 2017 Apr 19:ajprenal.00619.2016

PMID: 28424211

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