Role of angiotensin II in the transforming growth factor-beta 1 expression of rat kidney in anti-glomerular basement membrane antiserum-induced glomerulonephritis.
Induction of acute nephritis in the rat by injecting anti-glomerular basement membrane (GBM) antiserum is accompanied by a transient increase in angiotensin II generation in blood circulation within the first 24 h and a subsequent elevation of transforming growth factor-beta 1 (TGF-beta 1) mRNA levels in kidney cortex with a peak at days 7-8. Studies were carried out to determine whether the increased generation of angiotensin II plays a role in the elevation of TGF-beta 1 mRNA. Elevation of TGF-beta 1 mRNA levels 7 d after injection of antiserum was significantly 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 administration of this dose on day 0. In addition, angiotensin II infusion or 24 h at a rate of 50 ng/min did not alter the level of TGF-beta1 mRNA which was measured 6 d after the infusion. These results suggest that the anti-GBM antiserum-induced increase in TGF-beta 1 expression in the kidney is not responsible for angiotensin II generated in the blood circulation during the early phase of acute nephritis, but iis probably mediated by angiotensin II generated locally in the kidney.
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001485:Basement Membrane / Q000276:immunology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D005921:Glomerulonephritis / Q000276:immunology / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology*; D008297:Male; D011507:Proteinuria / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D012333:RNA, Messenger; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; C077793:candesartan cilexetil