Impairment by Hypoxia or Hypoxia/Reoxygenation of Nitric Oxide–Mediated Relaxation in Isolated Monkey Coronary Artery: the Role of Intracellular Superoxide

Journal of Pharmacological Sciences

Kazuhide Ayajiki³  Ayman Geddawy²  Kohei Yamamizu¹  Tomio Okamura²  Masashi Tawa²  Takashi Shimosato²  Takeshi Imamura² 

[1] Laboratory of Stem Cell Differentiation, Stem Cell Research Center, Institute for Frontier Medical Sciences, Kyoto University, Japan;Department of Pharmacology, Shiga University of Medical Science, Japan;Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Japan

关键词: hypoxia;    reoxygenation;    coronary artery;    nitric oxide;    superoxide;   

DOI  :  10.1254/jphs.11031FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(43)Cited-By(6)Supplementary materials(1)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]

【 授权许可】

Unknown