REGULATION OF MACULA DENSA NA-H EXCHANGE BY ANGIOTENSIN-II

Background: Angiotensin II (Ang II) is a positive modulator of tubulog lomerular feedback (TGF). At the present time, the site(s) at which An g II interacts with the signal transmission process remains unknown. I n certain renal epithelia, Ang II is known to stimulate apical Na:H ex change. Since macula densa cells possess an apical Na:H exchanger and Ang II subtype I receptors (AT(1)-receptors), we tested the possibilit y that Ang II might stimulate exchanger activity in these cells. Metho ds. Using the isolated perfused thick ascending limb with attached glo merulus preparation dissected from rabbit kidney, macula densa intrace llular pH (pH(i)) was measured with fluorescence microscopy using BCEC F. Results. Control pH(i), 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 pH(i) by 0.54 +/- 0.04 (N = 7, P < 0.01). A ng II (10(-9) M), added to the bath in the same paired experiments, si gnificantly elevated baseline pHi by 0.17 +/- 0.04, increased the magn itude of change in pH(i) (Delta = 0.71 +/- 0.05) and initial rate of a lkalinization (by 69%) to increased luminal [NaCl]. Ang II produced si milar effects when added exclusively to the luminal perfusate. In addi tion, 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. AT(1) bl ockade prevented the stimulatory but not the inhibitory effects of Ang II. Conclusion. Through the AT(1) Ang II may influence macula densa N a transport and regulate cell alkalinization via the apical Na:H excha nger. Thus, Ang II may modulate the TGF signal transmission process, a t least in part, through a direct effect on macula densa cell function .