1996 Fiscal Year Final Research Report Summary
ROLE OF MICROVASCULAR DISORDERS IN THE PATHOGENESIS OF MYOCARDIAL ISCHEMIA
| Project/Area Number |
06404034
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | KYUSHU UNIVERSITY FACULTY OF MEDICINE |
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Principal Investigator |
TAKESHITA Akira KYUSHU UNIVERSITY,FACULTY OF MEDICINE,PROFESSOR, 医学部, 教授 (30038814)
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| Co-Investigator(Kenkyū-buntansha) |
EGASHIRA Kensuke KYUSHU UNIVERSITY,FACULTY OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 講師 (60260379)
UENO Hikaru KYUSHU UNIVERSITY,FACULTY OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 講師 (50260378)
SHIMOKAWA Hiroaki KYUSHU UNIVERSITY,FACULTY OF MEDICINE,ASSOCIATE PROFESSOR, 医学部, 助教授 (00235681)
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| Project Period (FY) |
1994 – 1996
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| Keywords | angina pectoris / nitric oxide / endothelial cell / coronary circulation / serotonin / papaverine / angiotensin-converting enzyme inhibitor |
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| Research Abstract |
We have created animal models of microvascular disorders. Long-term inhibition of nitric oxide synthase with administering chronically an nitric oxide inhibitor (N^<omega>-nitro-L-arginine methyl ester, L-NAME) to rats and pigs caused coronary vascular structural changes (medial thickening and perivascular fibrosis). We examined whether microvascular responses to serotonin is altered in the pig model. After anesthesia, we infused serotonin into the coronary artery and found that the drug significantly decreased coronary blood flow in the L-NAME treated pigs but not in the control pigs.the vasomotor response to serotonin was similar between the two groups. Thus, these data suggest that the enhanced decrease in coronary blood flow to serotonin was due to augmented constriction of microvessels.
We aimed to provoke myocardial ischemia in the pig model. We administered papaverine into the coronary artery and found that the drug induced myocardial ischemia (myocardial lactate production). Because the papaverine-induced myocardial ischemia was associated with increased coronary blood flow, we concluded that the papaverine-induced myocardial ischemia was caused by altered distribution of regional myocardial blood flow.
We examined effects of L-arginine administration on endothelium-dependent coronary vasodilation in patients with microvascular angina and found that L-arginine supplementation improved acetylcholine-induced endothelium-dependent vasodilation in those patients. We also explored to determined the mechanism of bradykinin-induced coronary vasodilation in humans. We found that the bradykinin-induced coronary vasodilation was nearly completely inhibited by an inhibitor of NO synthesis and markedly augmented by an angiotensin-converting enzyme inhibitor enalaprilat.
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