Nicorandil improves glomerular injury in rats with mesangioproliferative glomerulonephritis via inhibition of proproliferative and profibrotic growth factors.
Recent clinical studies on chronic kidney disease (CKD) reported that renal dysfunction was a critical risk factor for cardiovascular events (CVE), which lead us to reconsider the effect of cardioprotective agents on the kidney. Glomerulonephritis, which is the major cause of CKD, is characterized by mesangial cell proliferation and extracellular matrix deposition. Nicorandil, a therapeutic drug for angina and acute heart failure, have been reported to show antiproliferative activity in mesangial cells. In this study, we first investigated the in vivo effects of nicorandil in anti-Thy1 nephritis rats. In male F344 rats, anti-Thy1 nephritis was induced by the injection of an anti-Thy1 antibody. From three days before induction, nicorandil (10, 30 mg/kg per day) was administered in the drinking water for 12 consecutive days. Anti-Thy1 nephritis resulted in a significant increase in proteinuria and glomerular mesangial cell proliferation. In nephritis rats, nicorandil (30 mg/kg per day) significantly suppressed increase in proteinuria, mesangial cell proliferation (the number of glomerular cell and glomerular area), and renal hypertrophy without affecting blood pressure. Nicorandil significantly prevented the overexpression of type I collagen, fibronectin, transforming growth factor (TGF)-beta, and platelet-derived growth factor (PDGF) mRNA. These results suggest that nicorandil may have renoprotective effects in mesangioproliferative glomerulonephritis.
Sudo
Hirokazu
H
Product Research Department, Chugai Pharmaceutical Co., Ltd., Japan.
Hirata
Michinori
M
Kanada
Hirotaka
H
Yorozu
Keigo
K
Tashiro
Yoshihito
Y
Serizawa
Ken-Ichi
K
Yogo
Kenji
K
Kataoka
Motoyuki
M
Moriguchi
Yoshiyuki
Y
Ishizuka
Nobuhiko
N
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects*; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D005353:Fibronectins / Q000378:metabolism; D015432:Glomerulonephritis, Membranoproliferative / Q000209:etiology / Q000517:prevention & control*; D007518:Isoantibodies; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020108:Nicorandil / Q000494:pharmacology* / Q000627:therapeutic use; D009929:Organ Size; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011507:Proteinuria / Q000517:prevention & control; D051381:Rats; D011916:Rats, Inbred F344; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D002316:Cardiotonic Agents; D024042:Collagen Type I; D005353:Fibronectins; D007518:Isoantibodies; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; C035678:anti-Thy antibody; D020108:Nicorandil