Connecting tubule glomerular feedback antagonizes tubuloglomerular feedback in vivo

Wang H, Garvin JL, D'Ambrosio MA, Ren Y, Carretero OA. Connecting tubule glomerular feedback antagonizes tubuloglomerular feedback in vivo. Am J Physiol Renal Physiol 299: F1374-F1378, 2010. First published September 8, 2010; doi:10.1152/ajprenal.00403.2010.-In vitro experiments showed that the connecting tubule (CNT) sends a signal that dilates the afferent arteriole (Af-Art) when Na+ reabsorption in the CNT lumen increases. We call this process CNT glomerular feedback (CTGF) to differentiate it from tubuloglomerular feedback (TGF), which is a cross talk between the macula densa (MD) and the Af-Art. In TGF, the MD signals the Af-Art to constrict when NaCl transport by the MD is enhanced by increased luminal NaCl. CTGF is mediated by CNT Na+ transport via epithelial Na+ channels (ENaC). However, we do not know whether CTGF occurs in vivo or whether it opposes the increase in Af-Art resistance caused by TGF. We hypothesized that CTGF occurs in vivo and opposes TGF. To test our hypothesis, we conducted in vivo micropuncture of individual rat nephrons, measuring stop-flow pressure (P-SF) as an index of glomerular filtration pressure. To test whether activation of CTGF opposes TGF, we used benzamil to block CNT Na+ transport and thus CTGF. CTGF inhibition with the ENaC blocker benzamil (1 mu M) potentiated the decrease in P-SF at 40 and 80 nl/min. Next, we tested whether we could augment CTGF by inhibiting NaCl reabsorption in the distal convoluted tubule with hydrochlorothiazide (HCTZ, 1 mM) to enhance NaCl delivery to the CNT. In the presence of HCTZ, benzamil potentiated the decrease in P-SF at 20, 40, and 80 nl/min. We concluded that in vivo CTGF occurs and opposes the vasoconstrictor effect of TGF.