Cation-Dependent and Cation-Independent Stages in Regulation of the Vascular Angiotensin Receptor after Alteration of Sodium Balance in the Rat*

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Abstract
The role of cations in vascular angiotensin receptor regulation has been investigated by radioligand receptor assay using a cell membrane fraction derived from mesenteric arterial muscle of the rat. In arterial membrane fractions from normal rats, the apparent receptor density varied with the ambient [Ca++] over the range, 0-10 mM. Receptor densities of 50 .+-. 4, 102 .+-. 4, and 156 .+-. 5 fmol/mg membrane protein were obtained in low (0 mM), normal (4.8 mM), and high (25 mM) [Ca++], respectively. After 2 days of sodium loading, sodium depletion, and converting enzyme blockade altered receptor densities were detected in normal assay but not in high [Ca++] or low [Ca++], indicating changes in the relationship between [Ca++] and apparent receptor density. Similar results were obtained after 12 days of sodium loading of converting enzyme blockade. After 12 days of sodium depletion, there was no difference in receptor density between normal and high [Ca++] (44 .+-. 5 fmol/mg protein) and the value obtained in low [Ca++] (27 .+-. 2 fmol/mg protein) was significantly below that for all other groups. No change in receptor affinity was observed. These results suggest that there are two stages in vascular angiotensin receptor regulation; an initial masking-unmasking process which involves Ca++, and with prolonged agonist occupancy, an actual loss of receptors.