Angiotensin II Vascular Receptors: Their Avidity in Relationship to Sodium Balance, the Autonomic Nervous System, and Hypertension

Hans R. Brunner; Paul Chang; Ronald Wallach; Jean E. Sealey; John H. Laragh

doi:10.1172/JCI106797

Angiotensin II Vascular Receptors: Their Avidity in Relationship to Sodium Balance, the Autonomic Nervous System, and Hypertension

Hans R. Brunner, Paul Chang, Ronald Wallach, Jean E. Sealey, and John H. Laragh

Published January 1, 1972 - More info

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Abstract

During intravenous administration of varying doses of angiotensin II antibody to anesthetized rats, apparently specific vascular receptors were characterized. These receptors compete with administered antibody to bind circulating angiotensin. This competitive phenomenon was used to evaluate the affinity of these receptors for angiotensin. Apparent vascular receptor affinity was defined by the amount of antibody required to block the blood pressure response to exogenous angiotensin. It was found that this receptor affinity varies directly with sodium intake so that the amount of antibody required to block was eightfold greater in normal animals on a high sodium intake, as compared with those on a low sodium intake. Sodium dependence of receptors was also demonstrated in nephrectomized animals, in desoxycorticosterone (DOC)-treated rats, and in chronic renal hypertension. Thus the observed changes in receptor affinity were usually inversely related to measured endogenous angiotensin II levels. Ganglionic blockade increased antibody requirement eightfold. All of these changes were consistent, with no overlap observed in response of individual animals from different groups. These results may explain the variation in pressor activity of angiotensin associated with changes in salt balance and ganglionic blockade.

In general, when sufficient antibody was injected to block the effect of exogenous angiotensin a blood pressure lowering effect was also observed. Two exceptions were the nephrectomized and the one-kidney renal hypertensive animals, in both of which antibody administration had no effect on blood pressure.

Additional results suggest that changes in receptor affinity are involved in the pathogenesis of various types of experimental hypertensions because the amount of antibody required to block angiotensin was enhanced in renal (twofold), DOC (fourfold), and genetic (fourfold) hypertension. Accordingly, changes in the affinity of these receptors could be critically involved in normal blood pressure control and in various forms of experimental and clinical hypertension, even when circulating angiotensin II levels are normal.