Hypertension, Vol 8, 600-605, Copyright © 1986 by American Heart Association
JM Wood, C Heusser, N Gulati, P Forgiarini and KG Hofbauer
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.
ARTICLES
Monoclonal antibodies against human renin. Blood pressure effects in the marmoset