EFFECTS OF CICAPROST AND FOSINOPRIL ON THE PROGRESSION OF RAT DIABETIC NEPHROPATHY

We have studied the effects of chronic therapy with cicaprost (a PGI(2 ) analog), fosinopril (a converting enzyme inhibitor), and the combina tion of both drugs on the progression of experimental diabetic nephrop athy. Uninephrectomized streptozotocin-induced diabetic rats were main tained for 8 months with plasma glucose between 13.7 and 22.0 mmol/L t o hasten renal damage. Systemic and renal parameters were measured per iodically, and at sacrifice structural and morphometrical renal studie s were performed to evaluate diabetic Control rats exhibited character istic features of this model, such as high blood pressure and plasma c reatinine and urinary albumin excretion, together with prominent alter ations in the kidney (renal and glomerular hypertrophies, mesangial ma trix expansion, and tubular alterations). The three therapies attenuat ed equivalently the progression of diabetic renal injury, as estimated by lower urinary albumin excretion, renal and glomerular hypertrophie s, and a better renal architectural preservation. No synergistic actio n was appreciated with the combined therapy. However, renal preservati on achieved with cicaprost was not linked to reductions in systemic bl ood pressure, whereas in the groups treated with fosinopril the hypote nsive effect of this drug could have contributed to the positive outco me of the therapy. Therefore, nephroprotection exerted by this PGI(2) analog in this model seems more related to the derangement of renal lo cal mechanisms than to systemic blood pressure control, Finally, the p ossibility that an impaired prostacyclin synthesis or bioavailability is involved in the pathogenesis of the diabetic nephropathy in this mo del underlies our results. (C) 1997 American Journal of Hypertension, Ltd.