Spironolactone suppresses inflammation and prevents L-NAME-induced renal injury in rats

Hirofumi Ikeda, Kazuhiko Tsuruya, Jiro Toyonaga, Kohsuke Masutani, Hideko Hayashida, Hideki Hirakata, Mitsuo Iida

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Abstract

Chronic inhibition of nitric oxide synthase by Nω-nitro- L-arginine methyl ester (L-NAME) causes progressive renal injury with systemic hypertension and interstitial macrophage infiltration. We have previously shown that there is local activation of the renin-angiotensin-aldosterone system in the renal cortex as a major pathogenic feature of macrophage infiltration. In this study, we measured the effects of the aldosterone antagonist, spironolactone, on renal injury in L-NAME-treated male Wistar rats. After 12 weeks of L-NAME-treatment, rats had increased systolic blood pressure, urinary protein excretion, and serum creatinine and histological analysis showed glomerulosclerosis, interstitial fibrosis, and macrophage infiltration. Treatment with spironolactone significantly prevented these renal changes, whereas treatment with hydralazine had no effect. The cortical expression of osteopontin was significantly elevated in L-NAME-treated rats, and expression of its mRNA significantly correlated with the number of infiltrating macrophages and degree of interstitial fibrosis. Spironolactone treatment markedly suppressed osteopontin expression. Our results suggest that reduced nitric oxide bioavailability caused renal inflammation and fibrosis through an aldosterone receptor-dependent mechanism associated with osteopontin expression independent of its systemic hemodynamic effects.

Original languageEnglish
Pages (from-to)147-155
Number of pages9
JournalKidney International
Volume75
Issue number2
DOIs
Publication statusPublished - Jan 2009

All Science Journal Classification (ASJC) codes

  • Nephrology

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    Ikeda, H., Tsuruya, K., Toyonaga, J., Masutani, K., Hayashida, H., Hirakata, H., & Iida, M. (2009). Spironolactone suppresses inflammation and prevents L-NAME-induced renal injury in rats. Kidney International, 75(2), 147-155. https://doi.org/10.1038/ki.2008.507