Activation of the Renin-Angiotensin System in Anti-glomerular Basement Membrane Antibody-Induced Glomerulonephritis

• Published in: Biological & pharmaceutical bulletin Vol. 18; no. 3; pp. 411 - 415
• Main Authors: HAYASHI, Kazumi, YAYAMA, Katsutoshi, SUZUKI, Yoshio, NAGAMATSU, Tadashi, OKAMOTO, Hiroshi, TAKANO, Masaoki, MATSUI, Takashi
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1995; Maruzen
• Subjects: angiotensin II receptor; Angiotensin Receptor Antagonists; angiotensinogen; Angiotensinogen - blood; Angiotensinogen - genetics; Animals; Antibodies - toxicity; Basement Membrane - immunology; Benzimidazoles - pharmacology; Biological and medical sciences; Biphenyl Compounds - pharmacology; Glomerular Mesangium - immunology; Glomerular Mesangium - ultrastructure; Glomerulonephritis; Glomerulonephritis - blood; Glomerulonephritis - immunology; Glomerulonephritis - physiopathology; Liver - metabolism; Male; Medical sciences; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Nephrotic Syndrome - drug therapy; Nephrotic Syndrome - physiopathology; Rats; Rats, Sprague-Dawley; renin; Renin - blood; Renin-Angiotensin System - drug effects; Renin-Angiotensin System - physiology; RNA, Messenger - metabolism; TCV-116; Tetrazoles; Glomerulonephritis; Urinary system disease; Rat; Peptide hormone; Rodentia; Renal disease; Vertebrata; Experimental disease; Renin angiotensin system; Mammalia; Animal; Peptidergic receptor; Angiotensin II
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.18.411

Activity of the reain-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 reain 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.