| Project/Area Number |
08670806
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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 | Hirosaki University |
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Principal Investigator |
OKUMURA Ken Hirosaki University, School of Medicine, Professor, 医学部, 教授 (20185549)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | nitric oxide / endothelium / coronary blood flow / adenosine / oxygen radicals / reactive hyperemia / L-arginine |
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| Research Abstract |
To clarify the role of endothelium-derived nitric oxide (EDNO) on the regulation of coronary blood flow, we performed in-vivo studies in anesthetized dogs. It was revealed that EDNO plays a role in the regulation of the basal coronary blood flow (Arch int Pharmacodyn 1994 ; 327 : 251-265), and that myocardial reactive hyperemia (RH) is mediated not only by adenosine but by EDNO (Am J Physiol 1992 ; 263 : H4-H14). Recently, we examined the effect of manganese (Mn)-superoxide dismutase (SOD) on RH in anesthetized dogs, and revealed superoxide redicals generated during ischemia for 60s and reperfusion attenuates myocardial RH through inactivation of EDNO (Cardiovascular Res 1996 ; 31 : 537-545).It was also shown that Mn-SOD shows more beneficial effects on myocardial RH than Cu, Zn-SOD.We also showed that when NO synthesis is inhibited by L-arginine analogue, LNAME,adenosine release is increased in response to the myocardial oxygen demand and with this compensatory adenosine release, coronary flow is increased and ventricular function is unaffected (Am J Physiol 1996 ; 270 : H427-H434). Chronic inhibition of NO formation with oral administration of L-NAME for 4 weeks blunted coronary reactive hyperemia but did not substantially impair the coronary blood flow response to the increased myocardial oxygen requirement produced by atrial pacing. It was therefore indicated that adenosine is likely to play a role also in chronic model of NO synthesis inhibition (Jpn Cric J,1998, in press).
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