title: Connecting tubule glomerular feedback antagonizes tubuloglomerular feedback in vivo.
abstract: 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 μM) 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.
authors.affiliation: Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan 48202, USA.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: J L
authors.initials: JL
authors.lastname: Garvin
authors.forename: M A
authors.initials: MA
authors.lastname: D'Ambrosio
authors.forename: Y
authors.initials: Y
authors.lastname: Ren
authors.forename: O A
authors.initials: OA
authors.lastname: Carretero
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D005246:Feedback / Q000187:drug effects*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000502:physiology*; D007684:Kidney Tubules / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009399:Nephrons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C013407:benzamil; D000584:Amiloride
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