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

ObjectiveTransforming growth factor-β (TGF-β) implicated in the pathogenesis of diabetic nephropathy. Hence, developing agents that antagonize fibrogenic signals is a critical issue facing researchers.Material and methodsFifty 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-β, aldosterone, creatinine and ACE. Degree of fibrosis was calculated.ResultsSerum creatinine, mean arterial blood pressure (MAP), aldosterone, ACE, TGF-β and renal fibrosis increased significantly in untreated diabetic hypertensive rats compared with control rats. Administration of spironolactone, moexpril, or both decreased these changes.ConclusionsAddition 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-β.