Activation of the renin-angiotensin system in anti-glomerular basement membrane antibody-induced glomerulonephritis.
Activity of the renin-angiotensin system in the nephrotic syndrome was investigated in rats with acute nephritis induced by anti-glomerular basement membrane (GBM) antibody. Injection of anti-GBM antibody resulted in a transient 2-fold elevation of both plasma renin and angiotensinogen with a peak at 12 h. Angiotensinogen mRNA levels in the liver also rapidly and transiently increased 4-fold at 3 h. The manifestation of acute nephritis, indicated by proteinuria, hypoalbuminemia, hypercholesterolemia and an increase in serum creatinine, following injection of anti-GBM antibody, was inhibited by a single administration of the selective angiotensin II type 1 receptor antagonist TCV-116 (1 mg/kg, p.o.) 2 h before an injection with the antibody, but not by successive administration of this drug for 1 week from 3 d after the injection of antibody. These results suggested that the enhanced generation of angiotensin II by elevated levels of both renin and its substrate in the early phase of anti-GBM nephritis promotes the evolution of acute nephritis via angiotensin II type 1 receptor.
Yayama
K
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Japan.
Matsui
T
T
Takano
M
M
Hayashi
K
K
Nagamatsu
T
T
Suzuki
Y
Y
Okamoto
H
H
D057911:Angiotensin Receptor Antagonists; D000808:Angiotensinogen / Q000097:blood / Q000235:genetics; D000818:Animals; D000906:Antibodies / Q000633:toxicity*; D001485:Basement Membrane / Q000276:immunology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000276:immunology* / Q000648:ultrastructure; D005921:Glomerulonephritis / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D008099:Liver / Q000378:metabolism; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles
D057911:Angiotensin Receptor Antagonists; D000906:Antibodies; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D012333:RNA, Messenger; D013777:Tetrazoles; D000808:Angiotensinogen; D012083:Renin; C077793:candesartan cilexetil