Peer-Reviewed Journal Details
Mandatory Fields
Wong PS, Johns EJ;
British Journal of Pharmacology
The receptor subtype mediating the action of angiotensin II on intracellular sodium in rat proximal tubules.
Optional Fields
1. An investigation was undertaken to explore the subtype of receptor involved in mediating the actions of angiotensin II on intracellular sodium content in suspensions of isolated proximal tubules of the rat. 2. Intracellular sodium content of the proximal tubules was measured with 23Na n.m.r. spectroscopy and under these conditions basal sodium content of the tubular cells was 69.04+/-1.73 nmol mg(-1) dry weight and the ATP levels, at 8.3+/-0.9 nmol ATP mg(-1) protein, were consistent with active respiration by the tissue. 3. In the presence of 10(-4) M PD123319, a selective non-peptide AT2 receptor antagonist, intracellular sodium levels rose from steady state by 30% (P < 0.01; n = 7) within 10 min of exposure to angiotensin II 10(-11) M. Over the subsequent 30 min steady state levels were re-established. Administration of angiotensin II 10(-11) M, in the presence of the selective AT1 receptor antagonist, losartan at either 10(-6) M (n = 5) or 10(-4) M (n = 6), was without effect on intracellular sodium levels, which were significantly different (P < 0.001) from those observed when PD 123319 was present. 4. Angiotensin II 10(-5) M, administered to the tubular suspension in the presence of 10(-4) M PD123319, decreased (P < 0.01, n = 6) intracellular 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 losartan 10(-4) M, angiotensin II 10(-5) M had no effect on intracellular sodium content which was markedly different (P < 0.001) from that obtained in the presence of PD123319. 5. These findings show that at both the high and low concentrations of angiotensin II, its modulation of intracellular sodium levels within the proximal tubule cells is mediated via the activation of AT1 receptors. The intracellular mechanism underlying this effect remain to be investigated.
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