Department of Physiology, School of Medicine, University of Southern California, Los Angeles.
J Exp Med. 1940 May 31;71(6):857-65. doi: 10.1084/jem.71.6.857.
Our results lead us to believe that renin in the form in which it is extracted from the kidney cannot be the agent causing chronic renal hypertension. The reasons against accepting renin as the pressor substance responsible for the hypertension of renal ischemia may be summed up as follows:- 1. The high blood pressure levels of renal ischemia cannot be approximated by any constant injection of renin that will maintain a sustained increase in normal animals. 2. The ratio of size of response to size of dose becomes progressively less as the amount of the dose is increased. If the hypertension of renal ischemia were due to a large elaboration of renin in the body, a small dose injected would be expected to have much less effect than in a normal individual. This is not the case; the response of the hypertensive animal to a given dose of renin is the same. Also animals with increased blood pressure due to a constant infusion of renin respond differently qualitatively and quantitatively to renin than do animals hypertensive from renal ischemia. 3. Since renin exhibits the phenomenon of tachyphylaxis one cannot explain the sustained hypertension of renal ischemia as due to a substance toward which the body becomes refractory as more and more of it is given. If tolerance results from the presence in the renin preparation of an antagonistic contaminant which persists longer in the body than the pressor agent, renal hypertension is definitely not caused by renin. This follows from our observations that rabbits hypertensive from renal ischemia, and in which tolerance is produced, maintain the blood pressure they had before injection of any renin.
我们的结果使我们相信，从肾脏中提取的肾素形式不可能是引起慢性肾性高血压的原因。不接受肾素作为引起肾缺血性高血压的加压物质的理由可以概括如下：- 1. 肾缺血引起的高血压水平不能通过任何持续注射肾素来近似，这种注射将维持正常动物的持续增加。2. 随着剂量的增加，反应大小与剂量大小的比值逐渐减小。如果肾缺血性高血压是由于体内大量产生肾素引起的，那么注射少量药物应该比在正常个体中产生的效果小得多。事实并非如此；高血压动物对给定剂量肾素的反应与正常个体相同。此外，由于持续输注肾素而导致血压升高的动物对肾素的反应在质和量上与由于肾缺血而导致高血压的动物不同。3. 由于肾素表现出脱敏现象，因此不能将肾缺血的持续高血压解释为由于身体对给予的物质变得越来越不敏感而引起的。如果耐受性是由于肾素制剂中存在一种拮抗污染物所致，而这种污染物在体内的持续时间比加压剂长，则肾性高血压肯定不是由肾素引起的。这是基于我们的观察结果，即由于肾缺血而产生高血压的兔子在注射任何肾素之前就保持了它们的血压。
