Active and passive immunization against angiotensin II in the rat and rabbit. Evidence for a normal regulation of the renin-angiotensin system.

Abstract

Active or passive immunization has been used repeatedly as a tool in studies on the role of the renin-angiotensin system in the control of blood pressure and kidney function. The results are not consistent among each other, and they are also at variance with other studies using different approaches. To evaluate the possible causes of these discrepancies, the biological characteristics of angiotensin antibodies were studied in rats. Following the intravenous injection of angiotensin II antibodies (purified by affinity chromatography), the plasma concentration of the antibodies declined in a two-exponential curve with half times of 11 hours and 7 days, which probably reflect distribution in the extracellular space and elimination, respectively. Plasma angiotensin II levels rose from preinjection levels of 100 pg/ml to 12,000 pg/ml within 10 minutes and then declined concomitantly with the decline in antibody concentration. We calculated that only a samll fraction of the circulating antibody was occupied by angiotensin II. Plasma renin concentrations were initially elevated both in controls and in antibody-injected rats, but they returned to the control level after 30 minutes and remained at that level throughout the rest of the experiment (10 days). This fact indicates that feedback mechanisms which control renin secretion, such as free plasma angiotensin II concentrations, are in the normal range. We therefore concluded that the renin-angiotensin system in antibody-injected rats was regulated at a normal level. Similar conditions seemed to exist in rabbits actively immunized against angiotensin II; these animals exhibited high concentrations of total immunoreactive angiotensin II (up to 200,000 pg/ml) and a small increase in plasma aldosterone and corticosterone concentrations.