[The effects of blocking intrarenal renin-angiotensin system on the expression of transforming growth factor-beta1 mRNA and extracellular matrix components].
OBJECTIVE
To explore the possible mechanism of benazepril in diminishing the progression of the renal diseases.


METHODS
Experimental glomerulosclerosis in rats was induced by adriamycin. The treated group was given benazepril (4 mg x kg(-1) x d(-1)). Intrarenal angiotensin converting enzyme (ACE) activity and angiotensin II (AngII) concentration were measured with colorimetry and radioimmunoassay respectively. Immunohistochemistry staining was employed for transforming growth factor beta1 (TGF beta1) and extracellular matrix (ECM) examination. To observe the expression of TGFbeta1 mRNA in the kidney, in situ hybridization was performed.


RESULTS
In the rats treated with benazeapril, ACE activity and Ang II concentration in renal tissue were significantly inhibited. In the meantime, expression of TGFbeta1 mRNA and TGFbeta1 protein were down-regulated, accompanied by decreasing accumulation of ECM (compared with the untreated rats, P < 0.01).


CONCLUSIONS
Benazepril plays an important role in down-regulating the expression of TGFbeta1 and decreasing the accumulation of ECM by blocking intrarenal renin-angiotensin system.
Zhou
C
C
Department of Nephrology, First Hospital, Beijing Medical University, Beijing 100034.
Li
J
J
Wang
H
H
D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D004317:Doxorubicin; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005921:Glomerulonephritis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D004317:Doxorubicin; D007703:Peptidyl-Dipeptidase A; C044946:benazepril