Bauer J, Berthold H, Schaefer F, Ehmke H, Parekh N
Departments of Physiology and Pediatrics, University of Heidelberg, D-69120 Heidelberg, Germany.
Am J Physiol. 1999 Aug;277(2):R412-8. doi: 10.1152/ajpregu.1999.277.2.R412.
The aim of the present study was to quantify with a uniform technique the rates of conversion of ANG I to ANG II in the lung and kidney and the degradation of both peptides to biologically inactive products in the pulmonary, renal, and systemic circulation. We infused the peptides intravenously, into the left ventricle, and into the left renal artery of rats and compared their effects on renal blood flow. The measured change in renal blood flow was used as a bioassay parameter to estimate the concentration of circulating ANG II. Mathematical analysis of our data allowed us to calculate conversion and degradation rates. Furthermore, the role of aminopeptidases A (EC 3.4.11.7) and N (EC 3.4.11.2) in the degradation of the peptides in the kidney was investigated by intrarenal infusion of the inhibitor amastatin. Our results show that the conversion rate of ANG I is 75% in the pulmonary and 21% in the renal circulation. Both peptides are degraded by 5% in the pulmonary, by 67% in the systemic, and by 93% in the renal circulation. Amastatin prevented 60% of the renal degradation of the peptides to inactive products, and this effect could be attributed to inhibition of aminopeptidase N. The results indicate that the converting capacity of the kidney is of minor importance for endocrine generation of ANG II but could be useful for the paracrine production.
本研究的目的是采用统一技术量化肺和肾中血管紧张素I(ANG I)向血管紧张素II(ANG II)的转化速率,以及这两种肽在肺循环、肾循环和体循环中降解为生物活性产物的速率。我们将这些肽静脉内、注入大鼠左心室以及左肾动脉,并比较它们对肾血流量的影响。所测得的肾血流量变化用作生物测定参数,以估计循环中ANG II的浓度。对我们的数据进行数学分析使我们能够计算转化和降解速率。此外,通过肾内注入抑制剂氨肽菌素,研究了氨肽酶A(EC 3.4.11.7)和氨肽酶N(EC 3.4.11.2)在肾中肽降解中的作用。我们的结果表明,ANG I在肺循环中的转化率为75%,在肾循环中为21%。两种肽在肺循环中降解5%,在体循环中降解67%,在肾循环中降解93%。氨肽菌素可防止60%的肽在肾中降解为无活性产物,这种作用可归因于对氨肽酶N的抑制。结果表明,肾的转化能力对于ANG II的内分泌生成不太重要,但可能对旁分泌产生有用。