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.