Skeggs L T
Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio.
Am J Hypertens. 1991 Oct;4(10 Pt 2):578S-583S. doi: 10.1093/ajh/4.10.578s.
It is known that the renin angiotension system as it is usually understood is not the mediator of experimental one-kidney, one-clip (1K,1C) hypertension in animals. There is also ample evidence that the blood pressure of dogs and rabbits with this form of hypertension can be lowered by immunization with hog renin, which implies that renin is the mediator. In an effort to resolve this contradiction, we searched for a second hypertensive substance which we thought may have been present in the crude hog kidney extracts that had been used to immunize the hypertensive animals. Instead, we ultimately discovered that the blood pressure of hypertensive rabbits could be lowered by immunization with pure hog renin. This remarkable finding could be explained if renin were transformed in vivo, exhibiting new antigenic sites and eliciting a second antihypertensive antibody. We found such an antibody. When free of antirenin, it lowered the blood pressure of 1K,1C hypertensive rabbits. The same antibody stained the cytoplasm of vascular smooth muscle cells and certain other cells in the tissues of normal and hypertensive rabbits. The presence of this transformed renin in the tissues of the rabbit was confirmed by chronic infusion of 125I-labeled renin into hypertensive rabbits. A significant portion of the radioactivity was found to be incorporated into a very high molecular weight, insoluble form. Its function in this location is unknown but must directly or indirectly involve vasoconstriction since its neutralization by specific antibody lowers the blood pressure of 1K,1C hypertensive rabbits.
众所周知，通常所理解的肾素血管紧张素系统并非动物实验性单肾单夹（1K，1C）高血压的介导因素。也有充分证据表明，患有这种高血压的犬类和兔类的血压可通过用猪肾素免疫来降低，这意味着肾素是介导因素。为了解决这一矛盾，我们寻找了第二种高血压物质，我们认为它可能存在于用于免疫高血压动物的粗制猪肾提取物中。相反，我们最终发现，用纯猪肾素免疫可降低高血压兔的血压。如果肾素在体内发生转化，表现出新的抗原位点并引发第二种抗高血压抗体，那么这一显著发现就可以得到解释。我们发现了这样一种抗体。在没有抗肾素的情况下，它可降低1K，1C高血压兔的血压。同样的抗体可使正常和高血压兔组织中的血管平滑肌细胞及某些其他细胞的细胞质染色。通过向高血压兔长期输注125I标记的肾素，证实了兔组织中存在这种转化的肾素。发现很大一部分放射性被整合到一种非常高分子量的不溶性形式中。其在该位置的功能尚不清楚，但必定直接或间接涉及血管收缩，因为其被特异性抗体中和会降低1K，1C高血压兔的血压。
