The mechanism by which
angiotensin-converting enzyme (
ACE) inhibitors prevent
proteinuria and glomerulosclerosis in experimental nephropathies is not yet clear. Experimental evidence is available that the effect of
ACE inhibitors on the glomerular function depends on the inhibition of
angiotensin II generation, but it is possible that inhibition of the
bradykinin breakdown also plays a relevant role. To establish the mediators of the effects of
ACE inhibitors in glomerular injury, we compared the effects of the
ACE inhibitor lisinopril with those of a specific
angiotensin receptor (AT1) antagonist (
ZD7155) on the renal function in male MWF/Ztm rats. After 4 months (end of the study), the untreated animals developed
hypertension and
proteinuria (160 +/- 10 mm Hg and 214 +/- 92 mg/24 h, respectively). In the
lisinopril- and in the ZD7155-treated rats, a comparable systolic pressure control was achieved (121 +/- 12 and 118 +/- 14 mm Hg, respectively), and
proteinuria was significantly prevented (averaging only 38 +/- 23 and 30 +/- 8 mg/24h, respectively) at the end of the study. The glomerular filtration rate was comparable in control and
lisinopril-treated rats and significantly increased in ZD7155-treated rats. Both treatments significantly reduced the glomerular capillary pressure and significantly increased the ultrafiltration coefficient (Kf) as compared with untreated animals. In ZD7155-treated rats the Kf was also significantly higher than in untreated animals glomerular
sclerosis and tubulointerstitital damage developed. Structural changes were absent in
lisinopril- and ZD7155-treated animals. These results show that the
antihypertensive and renal protective effects of
ACE inhibitors are shared by the
angiotensin receptor antagonist. Thus,
angiotensin II is the likely mediator of
proteinuria and glomerulosclerosis which develop spontaneously with age in this model.