In Vivo Inhibition of Renin by Antirenin Antibodies

Abstract

The use of antirenin antibody and Fab may provide a more specific physiologic tool and potential therapeutic agent than the existing pharmacologic inhibitors. The antibody combining site, by virtue of its larger size than organic compounds, has the capacity for a larger number of intramolecular contacts with its ligands, thus allowing increased selectivity and affinity. Renin-specific IgG and Fab obtained through immunization with purified dog renal renin have been studied. These agents had no effect on blood pressure in the sodium-replete conscious dog but induced systemic depressor responses in the sodium-depleted animal or during acute renovascular hypertension. These responses were accompanied with complete suppression of plasma renin and angiotensin II levels. Since antibodies and their fragments derived from immune sera are limited in their application to physiologic study with respect to lack of homogeneity, reproducibility, and limitation of quantity, monoclonal antibodies to purified human renal renin have also been obtained. Administration of monoclonal antibodies to conscious monkeys yielded similar overall cardiovascular responses as polyclonal antisera. These studies indicate that antirenin antibodies are highly potent and specific tools for physiologic studies and are of potential clinical usefulness.