2001 Fiscal Year Final Research Report Summary
Cardiac energy metabolism during development of hypertensive heart failure
| Project/Area Number |
12670655
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
NOZAWA Takashi Toyama Medical and Pharmaceutical University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (00180737)
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| Co-Investigator(Kenkyū-buntansha) |
ASANOI Hidetsugu Toyama Medical and Pharmaceutical University, Hospital, Assosiate Professor, 附属病院, 講師 (00150128)
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| Project Period (FY) |
2000 – 2001
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| Keywords | heart failure / metabolism / glucose / fatty acid / hypertrophy / rat / hypertension / insulin |
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| Research Abstract |
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.
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