ROLE OF ANGIOTENSIN-II IN THE TRANSFORMING GROWTH-FACTOR-BETA-1 EXPRESSION OF RAT-KIDNEY IN ANTIGLOMERULAR BASEMENT-MEMBRANE ANTISERUM-INDUCED GLOMERULONEPHRITIS

Induction of acute nephritis in the rat by injecting anti-glomerular b asement membrane (GEM) antiserum is accompanied by a transient increas e in angiotensin II generation in blood circulation within the first 2 4 h and a subsequent elevation of transforming growth factor-beta 1 (T GF-beta 1) mRNA levels in kidney cortex with a peak at days 7-8. Studi es were carried out to determine whether the increased generation of a ngiotensin II plays a role in the elevation of TGF-beta 1 mRNA, Elevat ion of TGF-beta 1 mRNA levels 7 d after injection of antiserum was sig nificantly inhibited by a successive daily administration of TCV-116, angiotensin II type 1 receptor antagonist, at 1 mg/kg/d from days 0 to 2 or from days 0 to 6, while it was not influenced by a single admini stration of this dose on day 0. In addition, angiotensin II infusion f or 24 h at a rate of 50 ng/min did not alter the level of TGF-beta 1 m RNA which was measured 6 d after the infusion. These results suggest t hat the anti-GEM antiserum-induced increase in TGF-beta 1 expression i n the kidney is not responsible for angiotensin II generated in the bl ood circulation during the early phase of acute nephritis, but is prob ably mediated by angiotensin II generated locally in the kidney.