Quantification of conversion and degradation of circulating angiotensin in rats.
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.
Bauer
J
J
Departments of Physiology and Pediatrics, University of Heidelberg, D-69120 Heidelberg, Germany.
Berthold
H
H
Schaefer
F
F
Ehmke
H
H
Parekh
N
N
D000626:Aminopeptidases / Q000378:metabolism; D000803:Angiotensin I / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D018826:CD13 Antigens / Q000378:metabolism; D005260:Female; D043384:Glutamyl Aminopeptidase; D006352:Heart Ventricles; D007262:Infusions, Intravenous; D007269:Injections, Intra-Arterial; D007668:Kidney / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012077:Renal Artery; D012079:Renal Circulation / Q000187:drug effects
D000804:Angiotensin II; D000803:Angiotensin I; D000626:Aminopeptidases; D018826:CD13 Antigens; D043384:Glutamyl Aminopeptidase