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

Abstract

OBJECTIVE:

Transforming 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 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-β, aldosterone, creatinine and ACE. Degree of fibrosis was calculated.

RESULTS:

Serum 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.

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-β.

• Authors: R H Mohamed, H R Abdel-Aziz, D M Abd El Motteleb, T A Abd El-Aziz
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 67 Issue 3 Pg. 209-14 (Apr 2013) ISSN: 1950-6007 [Electronic] France
• PMID: 20089379 (Publication Type: Journal Article)
• Copyright: Copyright © 2009 Elsevier Masson SAS. All rights reserved.

Chemical References

• Tetrahydroisoquinolines
• Transforming Growth Factor beta
• Spironolactone
• ras Proteins
• moexipril

Topics

• Animals
• Drug Therapy, Combination
• Hypertension, Renal (blood, drug therapy, pathology)
• Kidney (drug effects, physiology)
• Kidney Function Tests
• Male
• Nephritis (blood, drug therapy, pathology)
• Random Allocation
• Rats
• Rats, Wistar
• Spironolactone (administration & dosage)
• Tetrahydroisoquinolines (administration & dosage)
• Transforming Growth Factor beta (blood)
• ras Proteins (antagonists & inhibitors, metabolism)