Primate renins (human and monkey) are very similar. We used pure human renin to immunize marmosets (Calfithrirjacchus) and thereby produce a chronic blockade of the renin-angiotensinogen reaction. After a control period of 2 months, five male marmosets, on their usual sodium-poor diet, were immunized against pure human renin by three subcutaneous injections of 30 ,ug each, with complete and then incomplete Freund's adjuvant. Three The inhibition of the renin-angiotensin system at its first and rate-limiting step, the action of renin on angiotensinogen, can be achieved by the use of synthetic renin inhibitors (1) and by immunological tools. Indeed, the early studies on renin inhibition deal with passive or active immunization against renin (2-4). However, interpretation of such results is limited by the fact that renin was not completely purified. Thus, heterologous renin was used for immunization protocol, even though it is now known that renin has a very strong immunological specificity. Finally, only blood pressure was monitored in the earlier experiments, and no plasma renin activity or aldosterone assays were available. The renin antibody titer also could not be directly measured.The acute passive immunization of renovascular hypertensive dogs (5) and normotensive marmosets (6) with specific homologous renin antibodies clearly showed that the level of blood pressure depended on renin. From this latter study (6) it was concluded that renin regulated blood pressure in the normotensive marmoset ingesting its usual amount of sodium. The present study was designed to examine the effects of active immunization against renin in marmosets and to observe the effects of chronic blockade of the renin substrate reaction. (SBP) was also recorded once a week in unanesthetized animals by the tail-cuff method (BP recorder 8005, W+W Electronic, Appelex, Bagneux, France). The validation of the tail-cuff method for blood pressure measurement has been reported in normotensive (7) and hypertensive marmosets (8). Five marmosets were immunized by three repeated subcutaneous injections of 30 Ag of highly purified human renin (specific activity, 680 Goldblatt units per mg of protein). Purification was performed by immunoadsorption on a monoclonal antibody from ajuxtaglomerular cell tumor as described by Galen et al. (9). The first injections were performed in complete Freund's adjuvant (0.5 ml), the two others in incomplete Freund's adjuvant (0.5 ml). Three control animals received only the adjuvant. Injections were repeated at intervals of 3 weeks.
MATERIALS AND METHODSIn Vitro Experiments. The presence of renin antibodies was determined by the ability of marmoset plasma to bind pure human iodinated renin. The titer was defined as the antiserum dilution able to bind 50% of the renin tracer. Plasma renin concentration was measured by radioimmunoassay (RIA) of angiotensin I generated by 1 hr of incubation of 1:50-diluted marmoset plasma in the presence of an excess (635 pmol/200 gl) of human angiotensinogen (6). When the...