ACTIVATION OF THE RENIN-ANGIOTENSIN SYSTEM IN ANTIGLOMERULAR 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 (GEM) antibody. Injection of anti-GBM antibody resul ted in a transient 2-fold elevation of both plasma renin and angiotens inogen with a peak at 12 h. Angiotensinogen mRNA levers in the liver a lso rapidly and transiently increased 4-fold at 3 h. The manifestation of acute nephritis, indicated by proteinuria, hypoalbuminemia, hyperc holesterolemia and an increase in serum creatinine, following injectio n of anti-GEM antibody, was inhibited by a single administration of th e 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 successi ve 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 t he early phase of anti-GEM nephritis promotes the evolution of acute n ephritis via angiotensin II type 1 receptor.