Wood J M, Baum H P, Bews J P, Wachsmuth E D, Heusser C, Hofbauer K G
Biological Research Department, CIBA-GEIGY Limited Basle, Switzerland.
Clin Exp Hypertens A. 1987;9(8-9):1467-78. doi: 10.3109/10641968709158996.
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.
在本研究中，对一种抗人肾素单克隆抗体R-3-36-16在向灵长类动物长期给药期间的降压效果进行了研究。通过渗透微型泵连续腹腔内输注，以30或300微克/千克/天的剂量，将R-3-36-16给予食用低钠饮食的正常血压狨猴，持续14天。较低剂量对血压（BP）或血浆肾素活性（PRA）没有影响。治疗两天后，较高剂量使PRA降低了57%，并使BP降低了13±7毫米汞柱。尽管在治疗14天后降压反应持续存在（-17±2毫米汞柱），但PRA已恢复到治疗前水平。在停止治疗后的一周内，BP逐渐恢复到治疗前值。在停止长期治疗7周后给予R-3-36-16急性挑战剂量时，没有免疫反应的证据。因此，R-3-36-16在向缺钠灵长类动物长期给药期间似乎是一种有效且耐受性良好的降压药物。降压反应似乎与血浆中肾素的抑制没有直接关系。
