Effects of chronic administration of a monoclonal antibody against human renin in the marmoset.
In this study, the hypotensive efficacy of R-3-36-16, a monoclonal antibody against human kidney renin, was investigated during chronic administration to a primate. R-3-36-16 was given by continuous intraperitoneal infusion with osmotic minipumps to normotensive marmosets fed a low-sodium diet in doses of 30 or 300 micrograms/kg/day for 14 days. The lower dose had no effect on blood pressure (BP) or plasma renin activity (PRA). After two days of treatment, the higher dose reduced PRA by 57% and lowered BP by 13 +/- 7 mm Hg. Although the hypotensive response persisted after 14 days of treatment (-17 +/- 2 mm Hg), PRA had recovered to pretreatment levels. BP gradually returned to pretreatment values in the week after stopping the treatment. There was no evidence of an immune reaction when an acute challenge dose of R-3-36-16 was given 7 weeks after stopping the chronic treatment. Thus, R-3-36-16 appears to be an effective and well-tolerated hypotensive agent during chronic administration to sodium-depleted primates. The hypotensive response does not seem to be directly related to the inhibition of renin in the plasma.
Wood
J M
JM
Biological Research Department, CIBA-GEIGY Limited Basle, Switzerland.
Baum
H P
HP
Bews
J P
JP
Wachsmuth
E D
ED
Heusser
C
C
Hofbauer
K G
KG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D001794:Blood Pressure; D002144:Callithrix / Q000097:blood; D005260:Female; D006339:Heart Rate; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology; D008297:Male; D012083:Renin / Q000097:blood / Q000276:immunology*; D012982:Sodium, Dietary / Q000008:administration & dosage; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D012982:Sodium, Dietary; D012083:Renin