ACE inhibition reduces proteinuria, glomerular lesions and extracellular matrix production in a normotensive rat model of immune complex nephritis.
We studied the effect of the angiotensin converting enzyme (ACE) inhibitor, quinapril, on the clinical and morphological lesions of a normotensive model of immune complex nephritis. Untreated rats developed massive nephrotic syndrome, intense cell proliferation and glomerular and tubulointerstitial lesions. In the renal cortex of nephritic rats there was a significant increase in gene expression of TGF-beta 1, fibronectin and collagens, and ACE activity. Systolic blood pressure remained normal with progression of the disease. Administration of quinapril for three weeks to animals with glomerular lesions (proteinuria 20 to 50 mg/day) avoided the development of intense proteinuria (79 +/- 28 vs. 589 +/- 73 mg/day, P < 0.001) and decreased cell proliferation, glomerulosclerosis, tubulointerstitial lesions, and inflammatory infiltrates. Cortical gene expression of TGF-beta 1 and matrix proteins was also diminished. ACE activity was inhibited by 68% in renal cortex. These results show that quinapril administration to normotensive rats with immune complex nephritis decreases proteinuria and glomerular and tubulointerstitial lesions, probably modulating the local angiotensin II generation and its effects on cell growth, TGF beta and matrix protein synthesis.
Ruiz-Ortega
M
M
Renal Unit, Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain.
González
S
S
Serón
D
D
Condom
E
E
Bustos
C
C
Largo
R
R
González
E
E
Ortiz
A
A
Egido
J
J
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy*; D002455:Cell Division; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D015870:Gene Expression / Q000187:drug effects; D007546:Isoquinolines / Q000627:therapeutic use*; D009395:Nephritis, Interstitial / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011507:Proteinuria / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077583:Quinapril; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044005:Tetrahydroisoquinolines; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D012333:RNA, Messenger; D044005:Tetrahydroisoquinolines; D016212:Transforming Growth Factor beta; D007703:Peptidyl-Dipeptidase A; D000077583:Quinapril