Chronic administration of AM251 improves albuminuria and renal tubular structure in obese rats.
BACKGROUND Hypertension is the main risk factor for the progression of kidney damage in diabetes mellitus. The aim of the present work is to compare the effect of the treatment with irbesartan (IRBE) and omapatrilat (OMA), in obese Zucker rats (OZR). METHODS A group of 45 OZR were uninephrectomized to accelerate renal damage, and divided into three groups: two experimental groups (IRBE and OMA) treated with 50 and 40 mg/kg/d, respectively; and the control group (CG). At the end of the 8-month follow-up period, animals were killed and the remnant kidney was removed for histologic study and to evaluate the transforming growth factor-beta1 (TGF-beta1) expression. RESULTS Both therapies reduced blood pressure (BP) versus CG (P <.001). Moreover, systolic BP was significantly lower in the OMA group than in the IRBE group (P <.001). Also, both treatments significantly lowered the urinary albumin excretion (P <.001). The OMA treatment exhibited lower values than the IRBE treatment (P <.05). The kidney TGF-beta1 expression was reduced by both treatments to a similar level. The correlation between systolic BP and glomerulosclerosis (GS) is very high (r = 0.90; P <.0001). Also, a high correlation was observed between GS and proteinuria (r = 0.79, P <.0001). The correlation between systolic BP and proteinuria was weaker (r = 0.69; P <.01). CONCLUSIONS These data suggest that both therapies are effective in ameliorating the progression of renal damage in this experimental model. Omapatrilat affords greater long-term renoprotection than irbesartan, mainly due to its potent effect in reducing systolic BP.