THE RECEPTOR SUBTYPE MEDIATING THE ACTION OF ANGIOTENSIN-II ON INTRACELLULAR SODIUM IN RAT PROXIMAL TUBULES

1 An investigation was undertaken to explore the subtype of receptor i nvolved in mediating the actions of angiotensin II on intracellular so dium content in suspensions of isolated proximal tubules of the rat. 2 Intracellular sodium content of the proximal tubules was measured wit h Na-23 n.m.r. spectroscopy and under these conditions basal sodium co ntent of the tubular cells was 69.04 +/- 1.73 nmol mg(-1) dry weight a nd the ATP levels, at 8.3 +/- 0.9 nmol ATP mg(-1) protein, were consis tent with active respiration by the tissue. 3 In the presence of 10(-4 ) M PD123319, a selective non-peptide AT(2) receptor antagonist, intra cellular sodium levels rose from steady state by 30% (P<0.01; n = 7) w ithin 10 min of exposure to angiotensin II 10(-11) M. Over the subsequ ent 30 min steady state levels were re-established. Administration of angiotensin II 10(-11) M, in the presence of the selective AT(1) recep tor antagonist, losartan at either 10(-6) M (n=5) or 10(-4) M (n=6), w as without effect on intracellular sodium levels, which were significa ntly different (P<0.001) from those observed when PD 123319 was presen t. 4 Angiotensin II 10(-5) M, administered to the tubular suspension i n the presence of 10(-4) hi PD123319, decreased (P<0.01, n = 6) intrac ellular sodium content by 16% in the first 5 min, but in the following 25 min returned to steady state levels. However, in the presence of l osartan 10(-4) M, angiotensin II 10(-5) M had no effect on intracellul ar sodium content which was markedly different (P < 0.001) from that o btained in the presence of PD123319. 5 These findings show that at bot h the high and low concentrations of angiotensin II, its modulation of intracellular sodium levels within the proximal tubule cells is media ted via the activation of AT(1) receptors. The intracellular mechanism underlying this effect remain to be investigated.