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


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.
Mohamed
R H
RH
Medical biochemistry department, faculty of medicine, Zagazig university, 28-el-Galaa, Zagazig, Sharkia 44519, Egypt. randahussiny@yahoo.com
Abdel-Aziz
H R
HR
Abd El Motteleb
D M
DM
Abd El-Aziz
T A
TA
D000818:Animals; D004359:Drug Therapy, Combination; D006977:Hypertension, Renal / Q000097:blood* / Q000188:drug therapy / Q000473:pathology*; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D007677:Kidney Function Tests; D008297:Male; D009393:Nephritis / Q000097:blood* / Q000188:drug therapy / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000008:administration & dosage; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage; D016212:Transforming Growth Factor beta / Q000097:blood*; D018631:ras Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
D044005:Tetrahydroisoquinolines; D016212:Transforming Growth Factor beta; D013148:Spironolactone; D018631:ras Proteins; C058302:moexipril