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Cardiac energy metabolism during development of hypertensive heart failure

高血压心力衰竭发展过程中的心脏能量代谢

基本信息

批准号：
12670655
负责人：
NOZAWA Takashi
金额：
$ 2.11万
依托单位：
TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670655/
关键词：
heart failure metabolism glucose fatty acid hypertrophy rat hypertension insulin

项目摘要

In hypertrophic hearts, major myocardial energy substrate switches from fatty acid to glucose. However, myocardial contents of ATP and high-energy phosphates are reduced in cardiac hypertrophy. Therefore, a limited energy production in hypertrophied myocardium may contribute to the development of heart failure. The purpose of the present study was to investigate serial changes in myocardial fatty acid and glucose metabolism in Dahl salt-sensitive (DS) rats and salt-resistant (DR) rats.To evaluate cardiac fatty acid and glucose metabolism, quantitative dual-tracer autoradiography, using ^<131>I-9-methylpentadecanoic acid (9MPA), and ^<14>C-deoxyglucose (DG), was performed. Metabolic products of 9MPA were determined by a thin-layer chromatography and euglycemic hyperinsulinemic glucose clamp method was applied to determine insulin-stimulated glucose uptake. DS rats were developed to compensated LV hypertrophy at 12 weeks old, and advanced to heart failure at 18 weeks old. In contrast of DR rats, the major energy substrate switches from fatty acid to glucose with ages in DS rats. The ratio of 9MPA metabolites processed by β-oxidation to total myocardial uptake decreased with ages in DS rats, but was unchanged in DR rats. In 12 and 18 weeks old DS rats, the insulin-stimulated increases in DG uptake were markedly attenuated. Thus the capacity of fatty acid oxidation and insulin-stimulated glucose transport was already impaired in nonfailing hypertrophic heart.The present results suggest that a limited metabolic capacity of hypertrophied heart may play a role in a transition from compensated hypertrophy to heart failure.

在肥大的心脏中，主要的心肌能量底物从脂肪酸转变为葡萄糖。然而，心肌ATP和高能磷酸盐含量在心肌肥厚中减少。因此，肥厚心肌中有限的能量产生可能有助于心力衰竭的发展。本研究采用9 MPA和DG双示踪剂定量放射自显影技术，观察了盐敏感（DS）和盐耐受（DR）大鼠心肌脂肪酸和葡萄糖代谢的动态变化<131><14>。用薄层色谱法测定9 MPA的代谢产物，用正常血糖高胰岛素葡萄糖钳夹法测定胰岛素刺激的葡萄糖摄取。DS大鼠在12周龄时发展为代偿性左心室肥大，并在18周龄时发展为心力衰竭。与DR大鼠相反，DS大鼠的主要能量底物随着年龄的增长从脂肪酸转变为葡萄糖。DS大鼠β-氧化代谢产物占心肌总摄取的比例随增龄而降低，而DR大鼠无明显变化。在12和18周龄的DS大鼠中，胰岛素刺激的DG摄取增加明显减弱。因此，脂肪酸氧化和胰岛素刺激的葡萄糖转运的能力已经受损，在非衰竭肥厚的心脏。目前的结果表明，有限的代谢能力的肥厚的心脏可能在从代偿性肥大到心力衰竭的过渡中发挥作用。