J Peti-Peterdi1, P D Bell. 1. Department of Medicine, University of Alabama, Birmingham, USA.
Abstract
BACKGROUND: Angiotensin II (Ang II) is a positive modulator of tubuloglomerular feedback (TGF). At the present time, the site(s) at which Ang II interacts with the signal transmission process remains unknown. In certain renal epithelia, Ang II is known to stimulate apical Na:H exchange. Since macula densa cells possess an apical Na:H exchanger and Ang II subtype I receptors (AT1-receptors), we tested the possibility that Ang II might stimulate exchanger activity in these cells. METHODS: Using the isolated perfused thick ascending limb with attached glomerulus preparation dissected from rabbit kidney, macula densa intracellular pH (pHi) was measured with fluorescence microscopy using BCECF. RESULTS: Control pHi, during perfusion with 25 mM NaCl and 150 mM NaCl in the bath, averaged 7.22 +/- 0.02 (N = 24). Increasing luminal [NaCl] to 150 mM elevated pHi by 0.54 +/- 0.04 (N = 7, P < 0.01). Ang II (10(-9) M), added to the bath in the same paired experiments, significantly elevated baseline pHi by 0.17 +/- 0.04, increased the magnitude of change in pHi (delta = 0.71 +/- 0.05) and initial rate of alkalinization (by 69%) to increased luminal [NaCl]. Ang II produced similar effects when added exclusively to the luminal perfusate. In addition, low-dose Ang II (10(-9) M) stimulated while high-dose Ang II (10(-6) M) inhibited Na-dependent pH-recovery from an acid load. AT1 blockade prevented the stimulatory but not the inhibitory effects of Ang II. CONCLUSION: Through the AT1, Ang II may influence macula densa Na transport and regulate cell alkalinization via the apical Na:H exchanger. Thus, Ang II may modulate the TGF signal transmission process, at least in part, through a direct effect on macula densa cell function.
BACKGROUND: Angiotensin II (Ang II) is a positive modulator of tubuloglomerular feedback (TGF). At the present time, the site(s) at which Ang II interacts with the signal transmission process remains unknown. In certain renal epithelia, Ang II is known to stimulate apical Na:H exchange. Since macula densa cells possess an apical Na:H exchanger and Ang II subtype I receptors (AT1-receptors), we tested the possibility that Ang II might stimulate exchanger activity in these cells. METHODS: Using the isolated perfused thick ascending limb with attached glomerulus preparation dissected from rabbit kidney, macula densa intracellular pH (pHi) was measured with fluorescence microscopy using BCECF. RESULTS: Control pHi, during perfusion with 25 mM NaCl and 150 mM NaCl in the bath, averaged 7.22 +/- 0.02 (N = 24). Increasing luminal [NaCl] to 150 mM elevated pHi by 0.54 +/- 0.04 (N = 7, P < 0.01). Ang II (10(-9) M), added to the bath in the same paired experiments, significantly elevated baseline pHi by 0.17 +/- 0.04, increased the magnitude of change in pHi (delta = 0.71 +/- 0.05) and initial rate of alkalinization (by 69%) to increased luminal [NaCl]. Ang II produced similar effects when added exclusively to the luminal perfusate. In addition, low-dose Ang II (10(-9) M) stimulated while high-dose Ang II (10(-6) M) inhibited Na-dependent pH-recovery from an acid load. AT1 blockade prevented the stimulatory but not the inhibitory effects of Ang II. CONCLUSION: Through the AT1, Ang II may influence macula densa Na transport and regulate cell alkalinization via the apical Na:H exchanger. Thus, Ang II may modulate the TGF signal transmission process, at least in part, through a direct effect on macula densa cell function.
Authors: Kenneth E Bernstein; Frank S Ong; Wendell-Lamar B Blackwell; Kandarp H Shah; Jorge F Giani; Romer A Gonzalez-Villalobos; Xiao Z Shen; Sebastien Fuchs; Rhian M Touyz Journal: Pharmacol Rev Date: 2012-12-20 Impact factor: 25.468