Wood J M, Heusser C, Gulati N, Forgiarini P, Hofbauer K G
Hypertension. 1986 Jul;8(7):600-5. doi: 10.1161/01.hyp.8.7.600.
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.
在清醒、血容量减少的狨猴中研究了两种对灵长类肾素具有高结合亲和力的抗人肾素单克隆抗体的体内效应。这两种抗体，R-3-17-7和R-3-36-16，对肾素均具有高结合活性，但只有R-3-36-16在体外能抑制肾素的酶活性。在体内，静脉注射剂量高达100微克/千克的R-3-17-7后，虽然血浆肾素活性部分降低，但血压未受影响。相比之下，R-3-36-16在阈值剂量为3微克/千克时可引起血压降低并抑制血浆肾素活性。静脉注射10微克/千克的R-3-36-16后，观察到血压最大降幅以及血浆肾素活性完全抑制；这些效应持续长达2小时。用转换酶抑制剂预处理或肾切除可预防R-3-36-16的降压作用。相反，用R-3-36-16预处理可预防转换酶抑制剂的降压作用。这些发现表明，R-3-36-16诱导的降压反应完全是由于肾素-血管紧张素系统的阻断。因此，R-3-36-16似乎是灵长类肾素的一种特异性、强效和长效抑制剂。此类单克隆抗体为研究急性和慢性肾素阻断的作用提供了有趣的工具。
