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

Angiotensin II (AngII) enhances tubuloglomerular feedback responses and is considered to be a specific modulator of feedback activity. The sites at wh ich AngII interacts with the signal transmission process remain unknown. In certain renal epithelia, AngII stimulates Na/H exchange activities. Eviden ce for the regulation of macula densa apical Na/H exchange by AngII was rec ently reported. Because macula densa cells also express a basolateral Na/H exchanger, the possibility that AngII stimulates this exchanger activity wa s investigated. In preparations of isolated perfused thick ascending limb w ith attached glomerulus dissected from rabbit kidney, the intracellular pH (pH(i)) of macula densa cells was measured with fluorescence microscopy usi ng 2',7'-bis(2-carboxyethyl)-5-(and -6)carboxyfluorescein. Perfusion and ba thing solutions were iso-osmotic Cl-free Ringer's solutions modified using N-methyl-D-glucamine and cyclamate as the Na and Cl substitutes, respective ly. 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., basola teral solution) decreased pH(i) by 0.39 +/- 0.06 units (n = 5, P < 0.01). A ddition 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 acidificati on was completely blocked by coadministration of the AngII type 1 (AT(1)) r eceptor blocker candesartan (10(-8) M). In addition, AngII increased the ra te of pH(i) recovery from the acid load induced by readdition of bath Na. T his stimulatory effect of AngII was also completely reversed by coadministr ation of the AT(1) receptor blocker candesartan. These results indicate tha t AngII stimulates macula densa basolateral Na/H exchange via AT(1) recepto rs and therefore may affect tubuloglomerular feedback signal transmission, at least in part, through direct effects on macula densa transport processe s.