Abstract 520: Na/H Exchanger Participates in Tubuloglomerular Feedback
The afferent arteriole (Af-Art) accounts for most renal vasculature resistance, thus controlling glomerular filtration and renal function. The nephron regulates Af-Art resistance via two mechanisms, the vasoconstrictor tubuloglomerular feedback (TGF), initiated in the macula densa via Na/K/2Cl cotransporters (NKCC2), and the vasodilator connecting tubule glomerular feedback (CTGF), initiated in the connecting tubule via the epithelial Na channels (ENaC). However, when TGF and CTGF are inhibited by furosemide and benzamil, a novel form of TGF is observed.
We hypothesize that in addition to NKCC2, TGF can be initiated by Na/H exchangers (NHE). Furthermore, we hypothesize that when NKCC2 and NHE are blocked, CTGF causes Af-Art dilation.
In vivo, using the nephron micropuncture technique, we performed two consecutive stop-flow pressure (PSF) curves (an index of glomerular capillary pressure) by increasing the perfusion of the nephron from 0 to 40 nL/min while adding drugs to the tubular perfusate.
TGF was blocked by furosemide (vehicle -7.9±0.2 mmHg at 40 nL/min, furosemide -0.4±0.2; P<0.001). An NKCC2-independent form of TGF was revealed by blocking TGF with furosemide and CTGF with the ENaC inhibitor benzamil (furosemide: -0.2±0.1 mmHg, furosemide+benzamil: -4.3±0.3 mmHg, P<0.001). TGF was completely blocked by the combination of furosemide and the NHE inhibitor dimethylamiloride (DMA), resulting in vasodilatation (furosemide+DMA: 2.7±0.5 mmHg, n=6), that was blocked by CTGF inhibition (furosemide+DMA+benzamil: -1.1±0.2 mmHg, P<0.01, n=6).
We conclude that NHE in the nephron causes TGF when NKCC2 and ENaC are inhibited and that CTGF causes dilation of the Af-Art when TGF is completely blocked with NKCC2 and NHE inhibitors.
Author Disclosures: H. Wang: None. M.A. D’Ambrosio: None. Y. Ren: None. S. Monu: None. P. Leung: None. K. Kutskill: None. J.L. Garvin: None. E.L. Peterson: None. O.A. Carretero: None.
- © 2014 by American Heart Association, Inc.