Angiotensin II type I receptor antagonist suppresses proteinuria and glomerular lesions in experimental nephritis.
Angiotensin-converting enzyme inhibitors exert a beneficial effect on nephritis. We investigated the effects of KD3-671, an angiotensin AT1 receptor antagonist (2-propyl-8-oxo-1-[(2'-(H-tetrazole-5-yl)biphenyl-4-yl)methyl]-4,5,6,7-t etrahydro-cycloheptimidazole), on anti-glomerular basement membrane antibody-associated nephritis in rats. Untreated nephritic rats had massive proteinuria, glomerular lesions including crescent formation, a significant augmentation of proliferating cell nuclear antigen-positive cells, alpha-smooth muscle actin-positive cells, and the increase in deposition of proteoglycan, fibronectin and desmin in the glomeruli. Administration of KD3-671 to nephritic rats prevented the development of intense proteinuria, glomerular alterations and the increase in plasma urea nitrogen. KD3-671 suppressed the deposition of matrix protein and the expression of alpha-smooth muscle actin and desmin in the nephritic glomeruli. Captopril, an angiotensin-converting enzyme inhibitor, suppressed urinary protein excretion and the expression of desmin in the nephritic glomeruli, but not other parameters. These results suggest that KD3-671 may be a useful medicine against glomerulonephritis and glomerulosclerosis.
Nagamatsu
T
T
Department of Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Hayashi
K
K
Oka
T
T
Suzuki
Y
Y
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000473:pathology; D007093:Imidazoles; D007074:Immunoglobulin G / Q000096:biosynthesis; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000473:pathology; D008297:Male; D011507:Proteinuria / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
D057911:Angiotensin Receptor Antagonists; D016326:Extracellular Matrix Proteins; D007093:Imidazoles; D007074:Immunoglobulin G; C121117:KD3 671; D013777:Tetrazoles; D016212:Transforming Growth Factor beta