Systemic aldosterone, but not angiotensin II, plays a pivotal role in the pathogenesis of renal injury in chronic nitric oxide-deficient male rats

Takaichi Suehiro, Kazuhiko Tsuruya, Hirofumi Ikeda, Jiro Toyonaga, Shunsuke Yamada, Hideko Noguchi, Masanori Tokumoto, Takanari Kitazono

Research output: Contribution to journalArticle

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Abstract

Chronic inhibition of nitric oxide synthase by Nω-nitro-L-arginine methyl ester (L-NAME) causes progressive renal injury and systemic hypertension. Angiotensin II (Ang II) has been conventionally regarded as one of the primary causes of renal injury. We reported previously that such renal injury was almost completely suppressed by both an Ang II type I receptor blocker and an aldosterone antagonist. The aldosterone antagonist also inhibited the systemic Ang II elevation. Therefore, it remains to be elucidated whether Ang II or aldosterone directly affects the development of such renal injury. In the present study, we investigated the role of aldosterone in the pathogenesis of renal injury induced by L-NAME-mediated chronic nitric oxide synthase inhibition in male Wistar rats (aged 10 wk). Serial analyses demonstrated that the renal injury and inflammation in L-NAME-treated rats was associated with elevation of both Ang II and aldosterone. To investigate the direct effect of aldosterone on the renal injury, we conducted adrenalectomy (ADX) and aldosterone supplementation in L-NAME-treated rats. In ADX rats, aldosterone was undetectable, and renal injury and inflammation were almost completely prevented by ADX, although systemic and local Ang II and blood pressure were still elevated. Aldosterone supplementation reversed the beneficial effect of ADX. The present study indicates that aldosterone rather than Ang II plays a central and direct role in the pathogenesis of renal injury by L-NAME through inflammation, independent of its systemic hemodynamic effects.

Original languageEnglish
Pages (from-to)2657-2666
Number of pages10
JournalEndocrinology
Volume156
Issue number7
DOIs
Publication statusPublished - Jan 1 2015

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Aldosterone
Angiotensin II
Nitric Oxide
Kidney
NG-Nitroarginine Methyl Ester
Wounds and Injuries
Mineralocorticoid Receptor Antagonists
Inflammation
Nitric Oxide Synthase
Angiotensin I
Angiotensin Receptor Antagonists
Adrenalectomy
Wistar Rats
Hemodynamics
Blood Pressure
Hypertension

All Science Journal Classification (ASJC) codes

  • Endocrinology

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Systemic aldosterone, but not angiotensin II, plays a pivotal role in the pathogenesis of renal injury in chronic nitric oxide-deficient male rats. / Suehiro, Takaichi; Tsuruya, Kazuhiko; Ikeda, Hirofumi; Toyonaga, Jiro; Yamada, Shunsuke; Noguchi, Hideko; Tokumoto, Masanori; Kitazono, Takanari.

In: Endocrinology, Vol. 156, No. 7, 01.01.2015, p. 2657-2666.

Research output: Contribution to journalArticle

Suehiro, Takaichi ; Tsuruya, Kazuhiko ; Ikeda, Hirofumi ; Toyonaga, Jiro ; Yamada, Shunsuke ; Noguchi, Hideko ; Tokumoto, Masanori ; Kitazono, Takanari. / Systemic aldosterone, but not angiotensin II, plays a pivotal role in the pathogenesis of renal injury in chronic nitric oxide-deficient male rats. In: Endocrinology. 2015 ; Vol. 156, No. 7. pp. 2657-2666.
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