Angiotensin II directly stimulates macula densa Na-2Cl-K cotransport via apical AT1 receptors

Gergely Kovács, János Peti-Peterdi, László Rosivall, P. Darwin Bell

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Abstract

ANG II is a modulator of tubuloglomerular feedback (TGF); however, the site of its action remains unknown. Macula densa (MD) cells sense changes in luminal NaCl concentration ([NaCl]L) via a Na-2Cl-K cotransporter, and these cells do possess ANG II receptors. We tested whether ANG II regulates Na-2Cl-K cotransport in MD cells. MD cell Na+ concentration ([Na+]i) was measured using sodium binding benzofuran isophthalate with fluorescence microscopy. Resting [Na+]i in MD cells was 27.7 ± 1.05 mM (n = 138) and increased (Δ[Na+]i) by 18.5 ± 1.14 mM (n = 17) at an initial rate (Δ[Na+]i/Δt) of 5.54 ± 0.53 x 10-4 U/s with an increase in [NaCl]L from 25 to 150 mM. Both Δ[Na+]i and Δ[Na+]i/Δt were inhibited by 80% with 100 μM luminal furosemide. ANG II (10-9 or 10-12 M) added to the lumen increased MD resting [Na+]i and [NaCl]L-dependent Δ[Na+]i and caused a twofold increase in Δ[Na+]i/Δt. Bath (10-9 M) ANG II also stimulated cotransport activity, and there was no additive effect of simultaneous addition of ANG II to bath and lumen. The effects of luminal ANG II were furosemide sensitive and abolished by the AT1 receptor blocker candesartan. ANG II at 10-6 M failed to stimulate the cotransporter, whereas increased cotransport activity could be restored by blocking AT2 receptors with PD-123, 319. Thus ANG II may modulate TGF responses via alterations in MD Na-2Cl-K cotransport activity.

Original languageEnglish
Pages (from-to)F301-F306
JournalAmerican Journal of Physiology - Renal Physiology
Volume282
Issue number2 51-2
Publication statusPublished - Jun 29 2002

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Keywords

  • Angiotensin receptor blockade
  • Cytosolic sodium concentration
  • Fluorescent microscopy
  • Furosemide
  • Tubuloglomerular feedback

ASJC Scopus subject areas

  • Physiology
  • Urology

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