Abstract 118: Role of Connecting Tubule Glomerular Feedback in Tubuloglomerular Feedback Resetting After Unilateral Nephrectomy
Tubuloglomerular feedback (TGF) and connecting tubule glomerular feedback (CTGF) autoregulate nephronal afferent arteriolar resistance. In TGF, the macula densa signals the afferent arteriole to constrict when NaCl transport is enhanced by increased luminal NaCl, via sodium[[Unable to Display Character: –]]potassium-2-chloride cotransporter-2 (NKCC2). CTGF is mediated by connecting tubule sodium transport via epithelial sodium channel (ENaC) and dilates the afferent arteriole. Attenuation or resetting of TGF occurs after unilateral nephrectomy (UNX), but the mechanism behind this resetting remains unclear. This TGF resetting after UNX has been implicated in progressive glomerular damage due to sustained increase in glomerular capillary pressure. Since TGF is attenuated after UNX, we sought to test the hypothesis that CTGF is enhanced and that it contributes to TGF resetting after UNX. To test this hypothesis, we performed right side UNX in Sprague Dawley (SD) rats. 24 hours after surgery, we performed micropuncture of individual rat nephrons while measuring stop-flow pressure (PSF), which is an index of glomerular capillary pressure and afferent arteriolar tone. PSF decreases with an increase in afferent arteriolar tone. TGF response was measured as a decrease in PSF induced by switching late proximal perfusion from 0,10,20,30 and 40nl/min. Maximal TGF response was 1.3 ± 1.7 mmHg in UNX rats while 8.2 ± 0.9 mmHg in sham-UNX rats indicating a TGF resetting in UNX rats. When CTGF was inhibited with the ENaC blocker Benzamil (1μM), TGF response was 10±1.2 mmHg in UNX rats and 14.8± 1.3 mmHg in sham-UNX rats, indicating the restoration of TGF responses in UNX. We conclude that enhanced CTGF contributes to the TGF resetting after 24 hours of UNX. Enhanced CTGF may be responsible for glomerular damage post UNX.
Author Disclosures: S.R. Monu: None. H. Wang: None. Y. Ren: None. K. Kutskill: None. C. Romero: None. J. Juncos: None. B. Janic: None. E. Peterson: None. J. Garvin: None. O.A. Carretero: None.
- © 2015 by American Heart Association, Inc.