[Hypotensive effect of a human anti-renin monoclonal antibody (4G1D8) in the sodium-depleted alert marmoset].
A dose-response relationship was involved after an intravenous bolus of a human antirenin monoclonal antibody (4G1D8), in sodium depleted marmosets. The sodium depletion (furosemide: 30 mg/kg/d for 2 days) was used to potentiate the contribution of the renin-angiotensin system in the blood pressure (BP) control. To record BP and inject the antibody, 2 catheters were implanted the day before the experiment. The plasma renin activity (PRA) was measured by the RIA of angiotensin I after an incubation of plasmas for 1 hour at pH 7.4. The sodium depletion induced a dramatic increase of PRA (63.68 +/- 20.03 ng/ml/h of angiotensin I compared to 2.96 +/- 1.03; p less than or equal to 0.01; n = 13). The basal BP was 102.6 +/- 2.4 mmHg (n = 17). The maximal fall in BP was noted at about 30 min for the three groups of animals treated by 4G1D8; it was -7.5 +/- 4.3 mmHg at the dose of 0.01 mg/kg (n = 4), -21.3 +/- 3.8 mmHg (p less than or equal to 0.01) at 0.10 mg/kg (n = 4), and -27.5 +/- 1.4 mmHg (p = 0.10) at 0.24 mg/kg (n = 4). At the 0.10 and 0.24 mg/kg doses, the hypotension was lasting (greater than 3 h). PRA was strongly inhibited and HR was little modified. A dose-response relationship with a human antirenin monoclonal antibody, 4G1D8, provides a very interesting pharmacological model for a comparative study of renin inhibitors.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects*; D002144:Callithrix; D005260:Female; D005665:Furosemide / Q000008:administration & dosage; D008297:Male; D012083:Renin / Q000276:immunology / Q000502:physiology; D000092502:Renin Inhibitors
D000911:Antibodies, Monoclonal; D000959:Antihypertensive Agents; D005665:Furosemide; D012083:Renin; D000092502:Renin Inhibitors
Effet hypotenseur d'un anticorps monoclonal anti-rénine humaine (4G1D8) chez le marmouset vigile désodé.