Abstract
Blockade of the renin-angiotensin system has been established as a treatment for heart failure with hypertension and left ventricular hypertrophy, and for progressive kidney diseases. The present study was conducted to examine whether spironolactone, a mineralocorticold receptor antagonist, alone or in combination with cilazapril, an angiotensin converting enzyme (ACE) inhibitor, ameliorates proteinuria and renal lesions in an immune-initiated progressive nephritis model. Wistar rats were uninephrectomized 7 days before injection of anti-Thy-1 monoclonal antibody 1-22-3 to induce progressive glomerulonephritis. The nephritic rats were untreated or treated with spironolactone (400 mg/kg body weight/day), cilazapril (11 mg/kg body weight/day), or both for 10 weeks. Proteinuria was increased in the untreated rats 1 week after nephritis induction and was maintained throughout the experiment. Compared with the untreated animals (212.9± 49.2mg/day), proteinuria was significantly reduced in the spironolactone-treated group (62.0±4.0 mg/day, p=0.0046) and the cilazapril-treated group (71.8±26.0 mg/day, p=0.0048) on day 70 after antibody injection. Further reduction of proteinuria (42.4±4.5 mg/day, p=0.0019 vs. the untreated group) and less renal cortex interstitial fibrotic change (fibrosis score: 142.0±18.4 vs. 80.3±18.5 in the untreated group, p=0.0123) were detected in the spironolactone plus cilazapril-treated group. Blood pressure did not differ among the three treatment groups. In conclusion, spironolactone ameliorates proteinuria to the same degree as cilazapril, and concomitant use of spironolactone and an ACE inhibitor further suppresses renal disease progression. These data suggest that concomitant treatment with spironolactone and an ACE inhibitor has beneficial effects on immune-initiated progressive kidney disease.
| Original language | English |
|---|---|
| Pages (from-to) | 971-978 |
| Number of pages | 8 |
| Journal | Hypertension Research |
| Volume | 27 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 2004 Dec |
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Keywords
- Aldosterone
- Angiotensin-converting enzyme inhibitor
- Anti-Thy-1 nephritis
- Glomerulonephritis
- Spironolactone
ASJC Scopus subject areas
- Internal Medicine
Cite this
Spironolactone in combination with cilazapril ameliorates proteinuria and renal interstitial fibrosis in rats with anti-Thy-1 irreversible nephritis. / Asai, Masaki; Monkawa, Toshiaki; Marumo, Takeshi; Fukuda, Seiichi; Tsuji, Mihoko; Yoshino, Jun; Kawachi, Hiroshi; Shimizu, Fujio; Hayashi, Matsuhiko; Saruta, Takao.
In: Hypertension Research, Vol. 27, No. 12, 12.2004, p. 971-978.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Spironolactone in combination with cilazapril ameliorates proteinuria and renal interstitial fibrosis in rats with anti-Thy-1 irreversible nephritis
AU - Asai, Masaki
AU - Monkawa, Toshiaki
AU - Marumo, Takeshi
AU - Fukuda, Seiichi
AU - Tsuji, Mihoko
AU - Yoshino, Jun
AU - Kawachi, Hiroshi
AU - Shimizu, Fujio
AU - Hayashi, Matsuhiko
AU - Saruta, Takao
PY - 2004/12
Y1 - 2004/12
N2 - Blockade of the renin-angiotensin system has been established as a treatment for heart failure with hypertension and left ventricular hypertrophy, and for progressive kidney diseases. The present study was conducted to examine whether spironolactone, a mineralocorticold receptor antagonist, alone or in combination with cilazapril, an angiotensin converting enzyme (ACE) inhibitor, ameliorates proteinuria and renal lesions in an immune-initiated progressive nephritis model. Wistar rats were uninephrectomized 7 days before injection of anti-Thy-1 monoclonal antibody 1-22-3 to induce progressive glomerulonephritis. The nephritic rats were untreated or treated with spironolactone (400 mg/kg body weight/day), cilazapril (11 mg/kg body weight/day), or both for 10 weeks. Proteinuria was increased in the untreated rats 1 week after nephritis induction and was maintained throughout the experiment. Compared with the untreated animals (212.9± 49.2mg/day), proteinuria was significantly reduced in the spironolactone-treated group (62.0±4.0 mg/day, p=0.0046) and the cilazapril-treated group (71.8±26.0 mg/day, p=0.0048) on day 70 after antibody injection. Further reduction of proteinuria (42.4±4.5 mg/day, p=0.0019 vs. the untreated group) and less renal cortex interstitial fibrotic change (fibrosis score: 142.0±18.4 vs. 80.3±18.5 in the untreated group, p=0.0123) were detected in the spironolactone plus cilazapril-treated group. Blood pressure did not differ among the three treatment groups. In conclusion, spironolactone ameliorates proteinuria to the same degree as cilazapril, and concomitant use of spironolactone and an ACE inhibitor further suppresses renal disease progression. These data suggest that concomitant treatment with spironolactone and an ACE inhibitor has beneficial effects on immune-initiated progressive kidney disease.
AB - Blockade of the renin-angiotensin system has been established as a treatment for heart failure with hypertension and left ventricular hypertrophy, and for progressive kidney diseases. The present study was conducted to examine whether spironolactone, a mineralocorticold receptor antagonist, alone or in combination with cilazapril, an angiotensin converting enzyme (ACE) inhibitor, ameliorates proteinuria and renal lesions in an immune-initiated progressive nephritis model. Wistar rats were uninephrectomized 7 days before injection of anti-Thy-1 monoclonal antibody 1-22-3 to induce progressive glomerulonephritis. The nephritic rats were untreated or treated with spironolactone (400 mg/kg body weight/day), cilazapril (11 mg/kg body weight/day), or both for 10 weeks. Proteinuria was increased in the untreated rats 1 week after nephritis induction and was maintained throughout the experiment. Compared with the untreated animals (212.9± 49.2mg/day), proteinuria was significantly reduced in the spironolactone-treated group (62.0±4.0 mg/day, p=0.0046) and the cilazapril-treated group (71.8±26.0 mg/day, p=0.0048) on day 70 after antibody injection. Further reduction of proteinuria (42.4±4.5 mg/day, p=0.0019 vs. the untreated group) and less renal cortex interstitial fibrotic change (fibrosis score: 142.0±18.4 vs. 80.3±18.5 in the untreated group, p=0.0123) were detected in the spironolactone plus cilazapril-treated group. Blood pressure did not differ among the three treatment groups. In conclusion, spironolactone ameliorates proteinuria to the same degree as cilazapril, and concomitant use of spironolactone and an ACE inhibitor further suppresses renal disease progression. These data suggest that concomitant treatment with spironolactone and an ACE inhibitor has beneficial effects on immune-initiated progressive kidney disease.
KW - Aldosterone
KW - Angiotensin-converting enzyme inhibitor
KW - Anti-Thy-1 nephritis
KW - Glomerulonephritis
KW - Spironolactone
UR - http://www.scopus.com/inward/record.url?scp=20144369870&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20144369870&partnerID=8YFLogxK
U2 - 10.1291/hypres.27.971
DO - 10.1291/hypres.27.971
M3 - Article
VL - 27
SP - 971
EP - 978
JO - Hypertension Research
JF - Hypertension Research
SN - 0916-9636
IS - 12
ER -