| Project/Area Number |
14570646
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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, University Hospital, Assistant Professor, 附属病院, 講師 (00180737)
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| Co-Investigator(Kenkyū-buntansha) |
ASANOI Hidetsugu Toyama Medical and Pharmaceutical University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (00150128)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Heart failure / Hypertrophy / Sympathetic nerve / Fatty acid metabolism / Glucose metabolism / Cardiac metabolism |
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| Research Abstract |
We studied the effects of enarapril, angiotensin converting enzyme inhibitor, on cardiac metabolism during the development of hypertensive heart failure of Dahl salt sensitive rats. The, rats were fed a diet containing 8% NaCl after the age of 6 weeks that resulted in the development of compensated hypertrophy at 12 weeks of age, leading to heart failure by 18 weeks. Major energy substrate shifted from free fatty acid to glucose in rats with compensated hypertrophy and heart failure. However, β-oxidation of fatty acid was impaired and the capacity to increase cardiac glucose uptake during insulin stimulation markedly reduced in hypertrophied hearts prior to heart failure. In rats with heart failure, cardiac uptake of fatty acid reduced and the β-oxidation was impaired severer. Insulin stimulation did not increase glucose uptake any more.
Enarapril did not affect systolic blood pressure but attenuated the deterioration of left ventricular(LV) function assessed by LV dP/dt/P in rats with heart failure. Enarapril markedly improved the capacity to increase glucose uptake during insulin infusion at compensated hypertrophy. In rats with heart failure, enarapril inhibited the decrease in fttfty acid uptake and markedly increased glucose uptake at baseline before insulin infusion.
Thus, the effects of enarapril on hypertensive heart failure may, at least in part, result from changes in energy metabolism to more efficient energy production, i.e., glucose utilization. In our preliminary study using a microdialysis method, levels of LV interstitial norepinephrine were reduced by enarapril. Therefore, the inhibition of sympathetic nerve activity induced by enarapril may contribute to these favorable changes in cardiac energy metabolism.
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