Angiotensin II stimulates macula densa basolateral sodium/hydrogen exchange via type 1 angiotensin II receptors

Academic Article


  • Angiotensin II (AngII) enhances tubuloglomerular feedback responses and is considered to be a specific modulator of feedback activity. The sites at which AngII interacts with the signal transmission process remain unknown. In certain renal epithelia, AngII stimulates Na/H exchange activities. Evidence for the regulation of macula densa apical Na/H exchange by AngII was recently reported. Because macula densa cells also express a basolateral Na/H exchanger, the possibility that AngII stimulates this exchanger activity was investigated. In preparations of isolated perfused thick ascending limb with attached glomerulus dissected from rabbit kidney, the intracellular pH (pH(i)) of macula densa cells was measured with fluorescence microscopy using 2',7'-bis(2-carboxyethyl)-5-(and -6)carboxyfluorescein. Perfusion and bathing solutions were iso-osmotic Cl-free Ringer's solutions modified using N- methyl-D-glucamine and cyclamate as the Na and Cl substitutes, respectively. Control pH(i), during perfusion with 0 mM Na and 150 mM Na in the bath, averaged 7.21 ± 0.07 (n = 10). Removal of Na from the bath (i.e., basolateral solution) decreased pH(i) by 0.39 ± 0.06 units (n = 5, P < 0.01). Addition of 10-9 M AngII to the bath resulted in a significant increase in the Na-dependent acid load. This increase in Na-dependent cell acidification was completely blocked by coadministration of the AngII type 1 (AT1) receptor blocker candesartan (10-8 M). In addition, AngII increased the rate of pH(i) recovery from the acid load induced by readdition of bath Na. This stimulatory effect of AngII was also completely reversed by coadministration of the AT1 receptor blocker candesartan. These results indicate that AngII stimulates macula densa basolateral Na/H exchange via AT1 receptors and therefore may affect tubuloglomerular feedback signal transmission, at least in part, through direct effects on macula densa transport processes.
  • Authors

    Pubmed Id

  • 22957282
  • Author List

  • Bell PD; Peti-Peterdi J
  • Volume

  • 10
  • Issue

  • 1 SUPPL. 11