Dual effects of lisinopril on puromycin aminonucleoside nephrosis in unilaterally nephrectomized rats.
The therapeutic effects of angiotensin converting enzyme inhibitor, lisinopril, on puromycin aminonucleoside (PAN)-induced nephrosis were investigated using unilaterally nephrectomized rats. Lisinopril showed potent dual effects on PAN nephrosis. Lisinopril treatment (50 mg/l in drinking water) from day 5 or day 9 reduced urinary protein excretion and suppressed the development of glomerular sclerosis at 8 weeks after PAN injection (150 mg/kg, i.p.), indicating a therapeutic effect on the nephrosis. Recovery of decreased anionic charge sites on the glomerular basement membrane was involved, at least in part, in the therapeutic action of lisinopril against proteinuria. On the other hand, oliguria and progressive azotemia derived from continuous deterioration of the renal function was induced if the treatment of lisinopril was started on the same day as PAN injection. The renal dysfunction induced by simultaneous administration of lisinopril with PAN could be abolished by combination dosing with sarcosine, an angiotensin II (AII)-receptor agonist. These results indicate that lisinopril treatment attenuates proteinuria by ameliorating the anionic charge barrier on the glomerular basement membrane and that it also protects against the development of chronic renal disease with segmental glomerular sclerosis, although AII depletion during the acute nephrotic stage exacerbates the renal damage in PAN nephrosis of unilaterally nephrectomized rats.
Shinosaki
T
T
Shionogi Discovery Research Laboratories II, Shionogi & Co., Ltd., Osaka, Japan.
Takagawa
I
I
Sunagawa
N
N
Yonetani
Y
Y
Kurihara
H
H
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000633:toxicity*; D001485:Basement Membrane / Q000187:drug effects / Q000648:ultrastructure; D001835:Body Weight / Q000187:drug effects; D004347:Drug Interactions; D007274:Injections, Intraperitoneal; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D017706:Lisinopril / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity*; D008297:Male; D008854:Microscopy, Electron; D009392:Nephrectomy; D009401:Nephrosis / Q000139:chemically induced / Q000188:drug therapy*; D009846:Oliguria / Q000139:chemically induced; D011507:Proteinuria / Q000378:metabolism; D011691:Puromycin / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000819:agonists; D012521:Sarcosine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014511:Uremia / Q000139:chemically induced
D000806:Angiotensin-Converting Enzyme Inhibitors; D000900:Anti-Bacterial Agents; D011945:Receptors, Angiotensin; D011691:Puromycin; D017706:Lisinopril; D012521:Sarcosine