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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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