Downregulation of glomerular and vascular atrial natriuretic factor receptor subtypes by angiotensin II

We have previously reported that pressor doses of angiotensin II induce atrial natriuretic factor (ANF) release. Since the number of glomerular and vascular ANF receptors may vary inversely with plasma ANF levels, we investigated whether they are modified by angiotensin II. Male rats were infused intraperitoneally for 7 days with either a non-pressor (200 ng/kg per min) or a pressor (800 ng/kg per min) dose of angiotensin II. Sham-infused animals served as controls. Blood pressure and plasma C- and N-terminal ANF were higher, and atrial ANF concentrations lower, in pressor than in either non-pressor or sham-infused groups. Glomerular ANF receptor density was lower in pressor than in either non-pressor or sham-infused animals. The production of cyclic guanosine monophosphate by isolated glomeruli was significantly lower in pressor than in either non-pressor or sham-infused groups. Vascular ANF receptor density was lower in pressor than in either sham-infused or non-pressor rats. No difference in affinity was observed in any group for either glomerular or vascular ANF receptors. Neither the density nor the affinity of glomerular and vascular ANF receptors were affected by prior washing of the membranes with an acid solution (pH 5.0). Irreversible cross-linking of 125I-ANF followed by sodium dodecylsulfate-polyacrylamide gel electrophoresis in reducing conditions and autoradiography demonstrated that both high- and low-molecular weight receptors were downregulated in glomerular membranes, but only the low-molecular weight receptor was reduced in vascular membranes after a high-dose infusion of angiotensin II. We conclude that angiotensin II induces a true downregulation of its glomerular and vascular receptor subtypes, probably by increasing plasma ANF levels. A direct or indirect effect of angiotensin II on ANF receptor regulation cannot be eliminated, however.