| Project/Area Number |
62570388
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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 |
Circulatory organs internal medicine
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| Research Institution | Nagoya University |
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Principal Investigator |
ITO Takayuki (1988-1989) Nagoya University, School of Medicine, Assistant Professor, 医学部, 講師 (10111840)
小川 宏一 (1987) 名古屋大学, 医学部, 講師 (40023759)
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| Co-Investigator(Kenkyū-buntansha) |
OKUMURA Kenji Nagoya University, School of Medicine, Research Fellow, 医学部, 医員
HASHIMOTO Hidekazu Nagoya University, School of Medicine, Assistant, 医学部, 助手 (50172870)
OGAWA Kouichi Nagoya University, School of Medicine, Visiting, Assistant Professor, 医学部, 非常勤講師
伊藤 隆之 名古屋大学, 医学部, 助手 (10111840)
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| Project Period (FY) |
1987 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1989: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1988: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1987: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Atrial Fibrillation / c-GMP / ANP / Atrial Fibrillation Threshold / Atrial Pacing / Atrial Stretch / cーGMP / 心房ペーシング / 冠動脈 / C-GMP |
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| Research Abstract |
To investigate the role of cyclic nucleotides in the genesis and/or the persistence of atrial fibrillation (AF), plasma levels of cyclic GMP (c-GMP) and cyclic AMP (c-AMP) were measured in dogs with electrically induced AF. The atrial fibrillation threshold (AFT) after intravenous administration of a dibutyryl derivative of c-GMP (Dbc-GMP) on AFT were determined. Plasma levels of c-GMP, c-AMP and atrial natriuretic peptide (ANP) were also measured in patients during paroxysmal AF and sinus rhythm. The c-GMP level increased significantly 15 min after the onset of artificial AF, and gradually increased during the course of the experiment. Dbc-GMP induced a dose- dependent decrease in AFT. Clinical assessment revealed that patients had almost four times higher c-GMP and ANP levels during AF than during sinus rhythm. These results suggest that the increase in c-GMP plays an important role in the maintenance and/or the genesis of AF.
Plasma concentrations of ANP and c-GMP were significantly
… More
correlated with mean pulmonary arterial pressure and right atrial diameter in 89 patients with heart disease. It is suggested that increased plasma concentrations of ANP were induced by increased atrial pressure as well as atrial distention in human.
hANP relaxed canine coronary artery, and that increased tissue c-GMP levels in a dose-dependent fashion. The results suggest that hNAP relaxes the coronary artery by directly activating the guanylate cyclase in coronary smooth muscle.
The role of intracellular signals in the regulation of ANP release was investigated using isolated rat left atria. Dibutyryl cyclic AMP and dibutyryl cyclic GMP had no effect on ANP release. Arginine vasopressin and phenylephrine stimulated ANP release dose-dependently. The ANP release stimulated by phenylephrine was inhibited by W-7, a calmodulin antagonist, and H-7, a protein kinase C inhibitor. Atrial stretch stimulated ANP release, but the release was not inhibited by W-7 or H-7. These results suggest that the mechanism responsible for stretch-induced ANP release differs from that for phenylephrine-induced ANP release. Less
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