Renal expression of aminopeptidase A in rats with two-kidney, one-clip hypertension

Citation
G. Wolf et al., Renal expression of aminopeptidase A in rats with two-kidney, one-clip hypertension, NEPH DIAL T, 15(12), 2000, pp. 1935-1942
Citations number
23
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Urology & Nephrology
Journal title
NEPHROLOGY DIALYSIS TRANSPLANTATION
ISSN journal
0931-0509 → ACNP
Volume
15
Issue
12
Year of publication
2000
Pages
1935 - 1942
Database
ISI
SICI code
0931-0509(200012)15:12<1935:REOAAI>2.0.ZU;2-1
Abstract
Background. Angiotensin II (ANG II) is a major factor involved in the progr ession of chronic renal disease. Although the generation of this vasoactive peptide has been investigated in great detail, only a few studies have hit herto addressed the metabolism of ANG II into fragments such as angiotensin III and IV (ANG III, IV) which may exert physiological effects independent of ANG II. Aminopeptidase A (APA) is the major enzyme degrading ANG II. Th e aim of the current study was to evaluate glomerular APA expression in rat s with two-kidney, one-clip hypertension. Methods. The left renal artery was restricted with a 0.2-mm silver clip. Ki dneys were harvested 1 and 4 weeks after surgery. APA enzyme and protein ex pression was evaluated in kidney sections. Total APA enzyme activity and mR NA expression was assessed in isolated glomeruli. Degradation of exogenous ANG II by isolated glomeruli was measured with reverse-phase high-performan ce liquid chromatography. Results. APA enzyme activity, protein, and mRNA expression were stimulated in the clipped kidney 1 week after surgery compared with the contralateral kidney or normal controls. In contrast, 4 weeks after clipping APA activity and expression was higher in the contralateral kidney. In parallel to thes e findings, degradation of ANG II was greatest in isolated glomeruli obtain ed from the clipped kidney after 1 week. However, preparations from the con tralateral kidney 4 weeks after surgery were more active in the metabolism of exogenous ANG II. Conclusion. The present study provides evidence that APA is complexly regul ated in in vivo situations with an activated local renin-ANG II system. ANG II appears to play a direct role in this regulation. However, since conver sion of ANG II to ANG III by APA is the initial step leading to the formati on of ANG IV which may exert detrimental effects not mediated through class ical ANG II receptors, a local increase in APA activity may contribute to t he progression of chronic renal disease even during complete AT(1)-receptor blockade.