Ouabain stimulates atrial natriuretic peptide secretion via the endothelin-1/ET_B receptor-mediated pathway in beating rabbit atria

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• 作者：Li-ping Liu^a ; Lan Hong^a ; Li Yu^a ; Hai-yan Li^a ; Da-zhi Ding^c ; Shan-ji Jin^c ; Xun Cui^a ; ^b ; ^{cuixun@ybu.edu.cn}
• 关键词：Atrial natriuretic peptide ; Endothelin-1 ; Endothelin-1 receptor ; L-type Ca2+ channel ; Na+&ndash ; Ca2+ exchanger
• 刊名：Life Sciences
• 出版年：2012
• 期刊代码：62_00243205
• 类别：imm
• 出版时间：22 May, 2012
• 卷：90
• 期：19-20
• 页码：793-798
• 文件大小：925 K

摘要

Aims

Ouabain has been reported to increase the secretion of atrial natriuretic peptide (ANP) in vitro. However, the mechanism by which ouabain increases ANP secretion is not well known. Therefore, the purpose of the present study was to investigate the underlying mechanism of ouabain-stimulated ANP secretion.

Main methods

A perfused beating rabbit atrial model was used. The ANP and ET-1 levels in the atrial perfusates were measured by radioimmunoassays.

Key findings

Ouabain (1.0, 3.0 and 6.0 渭mol/L) significantly increased atrial ANP secretion in a dose-dependent manner, while the endothelin (ET)-1 levels were increased by the higher doses (3.0 and 6.0 渭mol/L) of ouabain. Ouabain-increased atrial ET-1 release was blocked by PD98059 (30.0 渭mol/L), an inhibitor of mitogen-activated protein kinase (MAPK). Nifedipine (1.0 渭mol/L), an inhibitor of L-type Ca²⁺ channels, completely abolished ouabain-increased ANP secretion without changing the ouabain-induced atrial dynamics. KB-R7943 (3.0 渭mol/L), an inhibitor of Na⁺-Ca²⁺ exchangers, completely blocked the effects of ouabain-increased atrial dynamics, but did not modulate ouabain-increased ANP secretion. ET-1 significantly stimulated atrial ANP release in a dose-dependent manner. The effects of ET-1 and ouabain on ANP secretion were completely blocked by BQ788 (0.3 渭mol/L), an inhibitor of ET-1 type B (ET_B) receptors, but not by BQ123 (0.3 渭M), an inhibitor of ET-1 type A receptors. Ouabain-increased atrial ANP secretion was blocked by PD98059 and indomethacin (30.0 渭mol/L), an inhibitor of cyclooxygenase.

Significance

Ouabain significantly stimulated atrial ANP secretion via an ET-1-ET_B receptor-mediated pathway involving MAPK signaling pathway activation and prostaglandin formation.