Michel J B, Sayah S, Guettier C, Reade R, Gardes J, Galen F X, Carelli C, Corvol P
INSERM U 36, Paris.
Arch Mal Coeur Vaiss. 1988 Jun;81 Spec No:281-90.
To block the renin-angiotensin system by antibodies directed against renin or angiotensins is an old and recent goal. This goal can be attained by passive transfer of antibodies or by active immunization against the different molecules of the system. Only passive transfer of polyclonal antibodies directed against the native substrate (angiotensinogen) has been performed in rats. This acute blockade of angiotensinogen substrate availability decrease blood pressure about 30 mmHg in salt depleted rats. Passive transfer of anti-converting enzyme immunoglobulins has been already performed in rabbit and rat. It induced an immunoallergic reaction in the pulmonary capillary bed. Immunization against angiotensin II has been a powerful tool in the exploration of the role of the renin angiotensin system in hypertension. Passive and active immunization have been performed in different species: rabbit, rat. The majority of the results concerning the decrease in blood pressure was negative. However, some works reported positive results which could be related to the high affinity of antibodies for angiotensins. Passive and active immunizations against renin were also performed in different species: dog, pig, rat, rabbit, primates. The majority of the results concerning the decrease of blood pressure were positive, if species specificity of renin was taken into account. Recently passive transfer of polyclonal and monoclonal antibodies, directed against human renin have been performed in normotensive and hypertensive primates, demonstrating an acute fall in blood pressure comparable to that observed with converting enzyme inhibitors. Active immunization against human renin has also been performed in primates; and the chronic blockade of the renin-substrate reaction obtained in this way was associated with a significant decrease in blood pressure, aldosterone secretion and a disappearance of plasma renin activity. Unfortunately, such an active immunization was associated with an organ specific autoimmune disease within the kidney. In conclusion, passive and active immunization against the different proteins and peptides of the system offers specific models of blockade which can be compared with synthetic inhibitors of renin, converting enzyme and angiotensins. Therapeutic application of this immunological approach necessitates the verification of the total absence of autoimmune disease.
通过针对肾素或血管紧张素的抗体来阻断肾素 - 血管紧张素系统是一个由来已久且近期仍在追求的目标。这一目标可通过抗体的被动转移或针对该系统不同分子的主动免疫来实现。在大鼠中仅进行了针对天然底物（血管紧张素原）的多克隆抗体的被动转移。这种对血管紧张素原底物可用性的急性阻断使盐缺乏大鼠的血压降低约30 mmHg。抗转化酶免疫球蛋白的被动转移已在兔和大鼠中进行。它在肺毛细血管床引发了免疫过敏反应。针对血管紧张素II的免疫已成为探索肾素 - 血管紧张素系统在高血压中作用的有力工具。被动和主动免疫已在不同物种中进行：兔、大鼠。关于血压降低的大多数结果是阴性的。然而，一些研究报告了阳性结果，这可能与抗体对血管紧张素的高亲和力有关。针对肾素的被动和主动免疫也在不同物种中进行：狗、猪、大鼠、兔、灵长类动物。如果考虑肾素的物种特异性，关于血压降低的大多数结果是阳性的。最近，针对人肾素的多克隆和单克隆抗体的被动转移已在正常血压和高血压灵长类动物中进行，显示出血压的急性下降与使用转化酶抑制剂时观察到的情况相当。针对人肾素的主动免疫也已在灵长类动物中进行；通过这种方式获得的肾素 - 底物反应的慢性阻断与血压显著降低、醛固酮分泌减少以及血浆肾素活性消失有关。不幸的是，这种主动免疫与肾脏内的器官特异性自身免疫疾病有关。总之，针对该系统不同蛋白质和肽的被动和主动免疫提供了可与肾素、转化酶和血管紧张素的合成抑制剂相比较的特异性阻断模型。这种免疫方法的治疗应用需要验证完全不存在自身免疫疾病。
