Effect of RAS inhibition on TGF-beta, renal function and structure in experimentally induced diabetic hypertensive nephropathy rats

Objective: Transforming growth factor-beta (TGF-beta) implicated in the pathogenesis of diabetic nephropathy. Hence, developing agents that antagonize fibrogenic signals is a critical issue facing researchers. Material and methods: Fifty rats were allocated to five groups: 1 = control rats, 2 = diabetic hypertensive rats 3 = diabetic hypertensive rats treated with spironolactone, 4 = diabetic hypertensive rats treated with moexpril, 5 = diabetic hypertensive rats treated with both spironolactone and moexpril. Measurement of TGF-beta, aldosterone, creatinine and ACE. Degree of fibrosis was calculated. Results: Serum creatinine, mean arterial blood pressure (MAP), aldosterone, ACE, TGF-beta and renal fibrosis increased significantly in untreated diabetic hypertensive rats compared with control rats. Administration of spironolactone, moexpril, or both decreased these changes. Conclusions: Addition of the spironolactone to moexpril was more effective in reducing fibrosis and improvement of renal function than monotherapy with either drug, possibly due to a dual inhibitory effect on the RAS, and thus suppression of TGF-beta. (C) 2009 Elsevier Masson SAS. All rights reserved.