Monoclonal antibodies against human renin. Blood pressure effects in the marmoset.

Abstract

The in vivo effects of two anti-human renin monoclonal antibodies with a high binding affinity for primate renin were studied in conscious, volume-depleted marmosets. These antibodies, R-3-17-7 and R-3-36-16, both have high binding activity for renin, but only R-3-36-16 inhibits the enzymatic activity of renin in vitro. In vivo, R-3-17-7 did not affect blood pressure after intravenous injection of doses up to 100 micrograms/kg, although plasma renin activity was partially reduced. In contrast, R-3-36-16 induced a reduction in blood pressure and an inhibition of plasma renin activity at a threshold dose of 3 micrograms/kg. The maximum fall in blood pressure and complete inhibition of plasma renin activity were observed after R-3-36-16, 10 micrograms/kg; these effects persisted for up to 2 hours. Pretreatment with a converting enzyme inhibitor or nephrectomy prevented the hypotensive effects of R-3-36-16. Conversely, pretreatment with R-3-36-16 prevented the hypotensive effects of a converting enzyme inhibitor. These findings indicate that the hypotensive response induced by R-3-36-16 is due entirely to blockade of the renin-angiotensin system. Thus, R-3-36-16 appears to be a specific, potent, and long-acting inhibitor of primate renin. Such monoclonal antibodies provide interesting tools for studying the effects of acute and chronic renin blockade.