Novel in vivo and in vitro mechanisms of positive inotropic effect of atractylodin.

IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Li Gao, Yuwei Wang, Wenhui Zhang, Xiaojia Zhu, Qianwen Gao, Yujie Xiao, Kesu Chen, Fuming Liu, Long Chen
{"title":"Novel in vivo and in vitro mechanisms of positive inotropic effect of atractylodin.","authors":"Li Gao,&nbsp;Yuwei Wang,&nbsp;Wenhui Zhang,&nbsp;Xiaojia Zhu,&nbsp;Qianwen Gao,&nbsp;Yujie Xiao,&nbsp;Kesu Chen,&nbsp;Fuming Liu,&nbsp;Long Chen","doi":"10.1111/1440-1681.13406","DOIUrl":null,"url":null,"abstract":"<p><p>This study was to investigate the inotropic effect of atractylodin and its underlying mechanism. The cardiac pressure-volume loop (P-V loop), Langendroff-perfused isolated rat heart, patch-clamp, Ca<sup>2+</sup> transient and western blot techniques were used. The results demonstrated that atractylodin (3 mg/kg, ip) remarkably increased the left ventricular stroke work, cardiac output, stroke volume, heart rate, ejection fraction, end-systolic pressure, peak rates of rise and fall of left ventricular pressures (+dP/dt<sub>max</sub> , -dP/dt<sub>max</sub> ), the slopes of end-systolic pressure-volume relationship (also named as end-systolic elastance, Ees) and reducing end-systolic volume and end-diastolic volume in the in vivo rat study. Also, atractylodin (3 mg/kg, ip) significantly decreased diastolic blood pressure and the arterial elastance (Ea) without significant systolic blood pressure change. In addition, atractylodin (0.1, 1, 10 µmol/L) also increased the isolated rat heart left ventricular developed pressure which is the difference between the systolic and diastolic pressure in non-pacing and pacing modes. Furthermore, JMV-2959 (1 μmol/L), a ghrelin receptor unbiased antagonist, blocked the increased left ventricular developed pressure of atractylodin in isolated rat hearts. Finally, atractylodin (5 µmol/L) increased the amplitude of Ca<sup>2+</sup> transient by enhancing SERCA2a activity, the sarcoplasmic reticulum Ca<sup>2+</sup> content and the phosphorylation of phospholamban at 16-serine. These results demonstrated that atractylodin had a positive inotropic effect by enhancing SERCA2a activity which might be mediated by acting ghrelin receptor in myocardium. In conclusion, atractylodin which had the positive inotropic effect and decreased diastolic blood pressure might serve as an agent for the treatment of heart failure in clinical settings.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"48 5","pages":"686-696"},"PeriodicalIF":2.5000,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/1440-1681.13406","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Experimental Pharmacology and Physiology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1111/1440-1681.13406","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/10/1 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 1

Abstract

This study was to investigate the inotropic effect of atractylodin and its underlying mechanism. The cardiac pressure-volume loop (P-V loop), Langendroff-perfused isolated rat heart, patch-clamp, Ca2+ transient and western blot techniques were used. The results demonstrated that atractylodin (3 mg/kg, ip) remarkably increased the left ventricular stroke work, cardiac output, stroke volume, heart rate, ejection fraction, end-systolic pressure, peak rates of rise and fall of left ventricular pressures (+dP/dtmax , -dP/dtmax ), the slopes of end-systolic pressure-volume relationship (also named as end-systolic elastance, Ees) and reducing end-systolic volume and end-diastolic volume in the in vivo rat study. Also, atractylodin (3 mg/kg, ip) significantly decreased diastolic blood pressure and the arterial elastance (Ea) without significant systolic blood pressure change. In addition, atractylodin (0.1, 1, 10 µmol/L) also increased the isolated rat heart left ventricular developed pressure which is the difference between the systolic and diastolic pressure in non-pacing and pacing modes. Furthermore, JMV-2959 (1 μmol/L), a ghrelin receptor unbiased antagonist, blocked the increased left ventricular developed pressure of atractylodin in isolated rat hearts. Finally, atractylodin (5 µmol/L) increased the amplitude of Ca2+ transient by enhancing SERCA2a activity, the sarcoplasmic reticulum Ca2+ content and the phosphorylation of phospholamban at 16-serine. These results demonstrated that atractylodin had a positive inotropic effect by enhancing SERCA2a activity which might be mediated by acting ghrelin receptor in myocardium. In conclusion, atractylodin which had the positive inotropic effect and decreased diastolic blood pressure might serve as an agent for the treatment of heart failure in clinical settings.

白术素正性肌力作用的新体内外机制。
本研究旨在探讨苍术素的肌力作用及其机制。采用心脏压力-容量环(P-V环)、langendroff灌注离体大鼠心脏、膜片钳、Ca2+瞬态和western blot技术。结果表明,白术素(3mg /kg, ip)可显著提高大鼠体内左室卒中功、心输出量、卒中容积、心率、射血分数、收缩压、左室压峰值上升和下降率(+dP/dtmax、-dP/dtmax)、收缩期末期压力-容积关系斜率(也称为收缩期末期弹性,Ees)以及收缩末期容积和舒张末期容积的减少。此外,苍术素(3mg /kg, ip)可显著降低舒张压和动脉弹性(Ea),而收缩压无明显变化。此外,白术素(0.1、1、10µmol/L)也增加了离体大鼠心脏左室发育压,即非起搏和起搏模式下的收缩压和舒张压之差。JMV-2959 (1 μmol/L)对白术素在离体大鼠心脏左室发育压力升高具有抑制作用。最后,白术素(5µmol/L)通过提高SERCA2a活性、肌浆网Ca2+含量和磷酸化蛋白16-丝氨酸来增加Ca2+瞬态振幅。上述结果表明,苍术素具有增强心肌组织SERCA2a活性的正性肌力作用,其机制可能与心肌组织中作用的胃饥饿素受体有关。综上所述,白术素具有正性肌力作用和降低舒张压的作用,可作为临床治疗心力衰竭的药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Clinical and Experimental Pharmacology and Physiology
Clinical and Experimental Pharmacology and Physiology PHARMACOLOGY & PHARMACY-PHYSIOLOGY
自引率
0.00%
发文量
128
期刊介绍: Clinical and Experimental Pharmacology and Physiology is an international journal founded in 1974 by Mike Rand, Austin Doyle, John Coghlan and Paul Korner. Our focus is new frontiers in physiology and pharmacology, emphasizing the translation of basic research to clinical practice. We publish original articles, invited reviews and our exciting, cutting-edge Frontiers-in-Research series’.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信