| Project/Area Number |
06671122
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Kidney internal medicine
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| Research Institution | Tohoku University |
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Principal Investigator |
MIURA Yukio Tohoku University, Graduate School of Information Science, Professor, 大学院情報科学研究科病態生理情報学, 教授 (90004689)
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| Co-Investigator(Kenkyū-buntansha) |
NOSHIRO Takao Tohoku University, School of Medicine, Assistant, 医学部附属病院, 助手 (40241624)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Congestive heart failure / Dopamine / Doxorubicin / Enalaprilat / Kidney / Norepinephrine spillover / Rabbit / congestive heart failure / dopamine / doxorubicin / enalaprilat / kidney / norepinephrine spillover / rabbit / dopamine spillover / dopamine excretion |
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| Research Abstract |
1. The acute effects of an angiotensin converting-enzyme inhibitor (ACEI), enalaprilat, on baroreflex-mediated changes in norepinephrine (NE) spillover rates in conscious rabbits with doxorubicin-induced cardiomyopathic heart failure (CHF).
After 4 weeks of doxorubicin, enalaprilat infusion led to a left shiftin the mean arterial pressure (MAP)-heart rate (HR) curve but no changes in renal and total NE spillover rates. After 6 weeks of doxorubicin treatment, when CHF was established, the control group showed blunted MAP-NE spillover responses. In the ACEI group, both MAP-renal NE and MAP-total NE spillover curves returned toward those seen in normal rabbits. The changes in the slopes of these curves were from 0.33 to 1.93 ng/min/mmHg for MAP-renal NE and from 1.75 to 3.57 ng/min/mmHg for MAP-total NE spillover curve.
These results indicate that enalaprilat restores baroreflex control of renal and total NE spillover in rabbits with CHF.This suggests that the renin-angiotensin system, possibly in the CNS,has an inhibitory effect on baroreflex-sympathetic reflex function in CHF.
2. ^3H-dopamine (DA) kinetics
The ^3H-DA metabolism during ^3H-DA infusion were determined by alumina extraction followed by high performance liquid chromatography. The ^3H-DA radioactivities in the arterial and the renal venous blood were 73(]SY.+-.])1% and 61(]SY.+-.])2% of the total radioactivity, respectively. The results suggest that the calculated DA spillover rates and DA clearance using ^3H-DA radioactivity determined only by alumina extraction were underestimated.
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