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肺动脉中的缺氧性血管收缩与细胞内钙离子:蛋白激酶C非依赖性钙离子致敏的证据

Hypoxic vasoconstriction and intracellular Ca2+ in pulmonary arteries: evidence for PKC-independent Ca2+ sensitization.

作者信息

Robertson T P, Aaronson P I, Ward J P

机构信息

Department of Medicine, St. Thomas' Hospital, London, United Kingdom.

出版信息

Am J Physiol. 1995 Jan;268(1 Pt 2):H301-7. doi: 10.1152/ajpheart.1995.268.1.H301.

DOI:10.1152/ajpheart.1995.268.1.H301
PMID:7840276
Abstract

The effect of hypoxia on intracellular Ca2+ ([Ca2+]i) and tension in small intrapulmonary arteries (IPA) of the rat was examined using the Ca2+ fluorophore fura 2. Induction of hypoxia in IPA preconstricted with 3 microM prostaglandin F2 alpha (PGF2 alpha) resulted in a biphasic contractile response, the first phase of which was associated with a transient rise in [Ca2+]i. No additional rise in [Ca2+]i was observed during the more slowly developing second phase constriction. Upon reoxygenation [Ca2+]i and tension returned to prehypoxic levels. Ro-31-8220 [a specific protein kinase C (PKC) inhibitor] reduced the first phase in IPA preconstricted with PGF2 alpha or 20 mM KCl, but had no effect on the second phase constriction in either of these groups. These results demonstrate that the first phase of the hypoxic constriction is associated with a transient rise in [Ca2+]i via either Ca2+ influx and/or release, and may have a PKC-dependent component, whereas the second phase involves a PKC-independent sensitization of the contractile machinery to Ca2+.

摘要

使用钙离子荧光探针fura 2检测了低氧对大鼠肺内小动脉(IPA)细胞内钙离子浓度([Ca2+]i)和张力的影响。在用3 microM前列腺素F2α(PGF2α)预收缩的IPA中诱导低氧,会产生双相收缩反应,其第一阶段与[Ca2+]i的短暂升高有关。在发展较为缓慢的第二阶段收缩过程中,未观察到[Ca2+]i的额外升高。复氧后,[Ca2+]i和张力恢复到低氧前水平。Ro-31-8220[一种特异性蛋白激酶C(PKC)抑制剂]可减弱用PGF2α或20 mM氯化钾预收缩的IPA中的第一阶段反应,但对这两组中的第二阶段收缩均无影响。这些结果表明,低氧收缩的第一阶段与通过钙离子内流和/或释放导致的[Ca2+]i短暂升高有关,可能有一个PKC依赖成分,而第二阶段涉及收缩机制对钙离子的PKC非依赖敏感化。

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