Adrenomedullin Administration Immediately After Myocardial Infarction Ameliorates Progression of Heart Failure in Rats

Author:

Nakamura Ryosai1,Kato Johji1,Kitamura Kazuo1,Onitsuka Hisamitsu1,Imamura Takuroh1,Cao Yuanning1,Marutsuka Kousuke1,Asada Yujiro1,Kangawa Kenji1,Eto Tanenao1

Affiliation:

1. From the First Department of Internal Medicine (R.N., J.K., K. Kitamura, H.O., T.I., Y.C., T.E.) and First Department of Pathology (K.M., Y.A.), Miyazaki Medical College, University of Miyazaki, Miyazaki, and Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka (K. Kangawa), Japan.

Abstract

Background— Adrenomedullin (AM) is expressed in cardiac tissue, and plasma AM levels increase in patients with acute myocardial infarction (MI). This study was performed to determine whether AM administration immediately after acute MI inhibits progression of heart failure in rats. Methods and Results— Rats were infused with 1.0 μg/h IP AM or saline over 7 days immediately after MI inducted by left coronary ligation and were examined 9 weeks after MI. Compared with the saline infusion, AM infusion significantly improved survival (59% versus 81%; P <0.05) and body weight gain (32%; P <0.01) and reduced heart weight (−28%; P <0.01), lung weight (−26%; P <0.01), left ventricular (LV) end-diastolic pressure (11.4±2.0 versus 4.0±0.6 mm Hg, mean± SEM; P <0.01), collagen volume fraction of noninfarcted LV (−39%; P <0.05), and plasma levels of endogenous rat AM (−38%; P <0.05) without affecting infarct size. To investigate the mechanism of AM actions, another series of MI rats infused with AM were killed on day 7. AM infusion had no effect on organ weights and hemodynamic parameters on day 7 of MI but significantly reduced urinary excretion of isoprostane (−61%; P <0.01) and noninfarcted LV mRNA levels of ACE (−31%; P <0.05) and p22-phox (−30%; P <0.05). Conclusions— AM administration during the early period of MI improved the survival and ameliorated progression of LV remodeling and heart failure. This beneficial effect was accompanied by reductions in oxidative stress and ACE mRNA expression in noninfarcted LV in the AM infusion period.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3