Impairment by Hypoxia or Hypoxia/Reoxygenation of Nitric Oxide–Mediated Relaxation in Isolated Monkey Coronary Artery: the Role of Intracellular Superoxide
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概要
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To investigate the effect of hypoxia or hypoxia/reoxygenation on vascular smooth muscle function, mechanical response of monkey coronary artery without endothelium was studied under normoxia, hypoxia, and hypoxia/reoxygenation. Hypoxia or hypoxia/reoxygenation impaired the relaxation by nitroglycerin or isosorbide dinitrate but not that by 8-bromoguanosine-3′,5′-cyclic monophosphate or isoproterenol. Tempol restored the impaired relaxation by nitroglycerin or isosorbide dinitrate, but superoxide dismutase had no effect. Apocynin, an NADPH oxidase inhibitor, improved the nitroglycerin-induced relaxation under hypoxia, but not under reoxygenation. Under combined treatment of apocynin with oxypurinol (xanthine oxidase inhibitor), rotenone (mitochondria electron transport inhibitor), or both, hypoxic impairment of vasorelaxation was restored more effectively. Similarly, impairment of the nitroglycerin-induced vasorelaxation under hypoxia/reoxygenation was restored by combined treatment with three inhibitors, apocynin, oxypurinol, and rotenone. Increase in superoxide production under hypoxia tended to be inhibited by apocynin and that under hypoxia/reoxygenation was abolished by combined treatment with three inhibitors. These findings suggest that increased intracellular superoxide production under hypoxia or hypoxia/reoxygenation attenuates vasodilation mediated with a nitric oxide/soluble guanylyl cyclase, but not adenylyl cyclase, signaling pathway. The main source of superoxide production under hypoxia seems to be different from that under reoxygenation: superoxide is produced by NADPH oxidase during hypoxia, whereas it is produced by xanthine oxidase, mitochondria, or both during reoxygenation.[Supplementary Figure: available only at http://dx.doi.org/10.1254/jphs.11031FP]
著者
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Okamura Tomio
Department Of Pharmacology
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Yamamizu Kohei
Laboratory Of Stem Cell Differentiation Institute For Frontier Medical Sciences Kyoto University
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Tawa Masashi
Department Of Pharmacology Shiga University Of Medical Sciences
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Shimosato Takashi
Department Of Pharmacology Shiga University Of Medical Sciences
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Imamura Takeshi
Department Of Applied Physics Faculty Of Science Tokyo Institute Of Technology:(present Address) Fuj
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Ayajiki Kazuhide
Department Of Pharmacology Shiga University Of Medical Science
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Geddawy Ayman
Department Of Pharmacology Shiga University Of Medical Science
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Yamamizu Kohei
Laboratory Of Stem Cell Differentiation Stem Cell Research Center Institute For Frontier Medical Sci
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Tawa Masashi
Department Of Pharmacology Shiga University Of Medical Science
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Shimosato Takashi
Department Of Pharmacology Shiga University Of Medical Science
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