Effect of Diadenosine Tetraphosphate (AP_4A) on Coronary Arterial Microvessels in the Beating Canine Heart
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概要
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Diadenosine tetraphosphate (AP_4A) can be released from activated platelets and the present study examined its effect on coronary arterial microvessels. The role of purinoceptors in the coronary microcirculation in vivo was als investigated. In open chest dogs, coronary arterioles were observed using a microscope with a floating objective. In Protocol 1, AP_4A (1, 10, 100 and 1,000μmol/L) was superfused onto the heart surface before and during the superfusion of 10μmol/L of 8-phenyltheophyline (8-PT), a P_1 purinoceptor blocker. In Protocol 2, AP_4A (0.1, 1, 10, and 100nmol・kg^<-1>・min^<-1>) was infused into the left anterior descending coronary artery before and during the superfusion of 10μmol/L of 8-P. In addition to 8-PT, 30μmol/L of pyridoxalphosphate-6-azophenyl 2', 4'-disulphonic acid (PPADS), a P2x purinoceptor blocker in Protocol 3, or 300μmol/L of N^w-nitro-L-arginine (LNNA) in Protocol 4, was continuously superfused, and 4 doses of AP_4A were cumulatively superfused as in Protocol 1. In Protocol 5, 10μmol/L of α, β-methylene ATP, an agonist of P2x purinoceptors, was superfused for 60 min. Superfused AP_4A dilated arterio;es in a dose-dependent manner. The magnitude of dilatation was greater in smaller arterioles (small vessel <ge;150μm: 24.5±2.2% vs large vessel > 150μm: 10.6±1.5% at a dose of 1,000 μmol/L, p<0.001). On the other hand, intraluminally appled AP_4A also dilated arterioles, but no size dependency was shown. In the presence of 8-PT, vasodilatory responses to superfused and intraluminally applied AP_4A were attenuated and the lower doses of AP_4A constricted arterioles. This vasoconstrictor effect was not affected by PPADS. The vasodilatory effect of the higher doses of AP_4A was almost abolished in the presence of LNNA. α, β-methylene ATP had no effect on coronary microvascular diameters. AP_4A has bidirectional effects on coronary arterial microvessels: vasodilatory effects mediated by P_1 purinoceptors and NO, which might be mediated by P_<2Y> purinoceptors, and a vasoconstrictor effect, which is not mediated by P_<2X> purinoceptors.
- 社団法人日本循環器学会の論文
- 2000-10-20
著者
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Shirato Kunio
The First Department of Internal Medicine, Tohoku University School of Medicine
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Shirato Kunio
The First Department Of Internal Medicine Tohoku University School Of Medicine
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Kanatsuka Hiroshi
The First Dept. of Internal Medicine, Tohoku University School of Medicine
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Kanatsuka Hiroshi
Department Of Comprehensive Medicine Tohoku University Hospital
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Sugimura Akihiko
The First Department Of Internal Medicine Tohoku University School Of Medicine
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Tanikawa Toshinori
The First Department of Internal Medicine, Tohoku University, School of Medicine
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Ong Boon
The First Department of Internal Medicine, Tohoku University, School of Medicine
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Ong Boon
The First Department Of Internal Medicine Tohoku University School Of Medicine
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Kanatsuka Hiroshi
The First Department Of Internal Medicine Tohoku University School Of Medicine
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Kanatsuka Hiroshi
First Dept Of Internal Medicine Tohoku University School Of Medicine
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Kanatsuka Hiroshi
Department Of Comprehensive Medicine Tohoku University School Of Medicine
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Tanikawa Toshinori
The First Department Of Internal Medicine Tohoku University School Of Medicine
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Shirato Kunio
The First Department of Internal Medicine, Tohoku University, School of Medicine
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