EFFECTS OF UP269-6, A NEW ANGIOTENSIN-II RECEPTOR ANTAGONIST, AND CAPTOPRIL ON THE PROGRESSION OF RAT DIABETIC NEPHROPATHY

To estimate the effects of UP269-6, a nonpeptide angiotensin II recept or antagonist, and captopril, a converting enzyme inhibitor, on the pr ogression of nephropathy, 77 uninephrectomized diabetic rats were main tained for 8 months with plasma glucose levels from 300 to 500 mg/dL. Systemic and renal parameters were periodically measured, and, at the time of death, a histological evaluation of renal damage was performed . Control rats (no additional treatment but insulin) showed increased blood pressure and urinary albumin levels, together with prominent alt erations in the kidney (renal and glomerular hypertrophies, tubular at rophy, and 19% of sclerotic glomeruli). Captopril (50 mg/kg/day) and U P269-6 (10 mg/kg/day) reduced blood pressure and albumin excretion lev els, and improved histological renal preservation (lower renal and glo merular hypertrophies, tubular atrophy, and percentage of sclerotic gl omeruli: 5% and 7%, respectively). Finally, a low dose of UP269-6 (1 m g/kg/day), which induced an intermediate level of blood pressure betwe en control and the other treated groups, produced an equivalent degree of nephroprotection. Our data demonstrate the efficacy of this new an giotensin II receptor antagonist on the progression of diabetic renal damage. These results also reinforce the role attributed to angiotensi n II in the development of renal derangement in this model, as UP269-6 is devoid of agonistic effect on the kinin system. (C) 1997 American Journal of Hypertension, Ltd.