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) inhib itor, quinapril, on the clinical and morphological lesions of a normot ensive model of immune complex nephritis. Untreated rats developed mas sive nephrotic syndrome, intense cell proliferation and glomerular and tubulointerstitial lesions. In the renal cortex of nephritic rats the re was a significant increase in gene expression of TGF-beta 1, fibron ectin and collagens, and ACE activity. Systolic blood pressure remaine d 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 v s. 589 +/- 73 mg/day, P < 0.001) and decreased cell proliferation, glo merulosclerosis, tubulointerstitial lesions, and inflammatory infiltra tes. Cortical gene expression of TGF-beta 1 and matrix proteins was al so diminished. ACE activity was inhibited by 68% in renal cortex. Thes e results show that quinapril administration to normotensive rats with immune complex nephritis decreases proteinuria and glomerular and tub ulointerstitial lesions, probably modulating the local angiotensin II generation and its effects on cell growth, TGF beta and matrix protein synthesis.