PULMONARY ARTERIAL HYPOXIC CONTRACTION - SIGNAL TRANSDUCTION
PULMONARY ARTERIAL HYPOXIC CONTRACTION - SIGNAL TRANSDUCTION
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DOI：
10.1152/ajplung.1992.263.1.l73
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发表时间：
1992-07-01
影响因子：
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通讯作者：
RHOADES, RA
中科院分区：
文献类型：
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作者：
JIN, NJ;PACKER, CS;RHOADES, RA
先前报道离体大鼠肺动脉对急性缺氧的反应是双相的，包括最初的短暂快速收缩，随后部分松弛（第一阶段），然后是第二次缓慢发展但持续的收缩（第二阶段）。本研究的目的是确定以下内容：1) 是否需要内皮产物，2) 细胞外和/或细胞内钙或蛋白激酶 C 是否可能是介导肺动脉缺氧收缩的第二信使，以及 3) 是否需要鸟苷 3',5'-环单磷酸 (cGMP)、内皮源性舒张因子 (EDRF)、前列腺素 I2 (PGI2) 或 A2腺苷受体激活参与第一相松弛。无 Ca2+ 介质和维拉帕米（一种 Ca2+ 通道阻滞剂）都不会改变第 1 相收缩，但第 2 相收缩被这些治疗中的任何一种所消除。 Ryanodine（一种肌浆网 Ca2+ 消耗剂）对 1 期收缩没有影响。 H-7（一种 PKC 抑制剂）抑制 2 相收缩，而对 1 相收缩没有影响。去除内皮消除了无 Ca2+ 介质或正常 Ca2+ 介质中的 1 相收缩，但没有改变 2 相收缩或 1 相松弛。亚甲蓝（鸟苷酸环化酶抑制剂）、N（omega）-硝基-L-精氨酸（EDRF 阻滞剂）、乙酰水杨酸（环氧合酶抑制剂）、黄嘌呤氨基同源物（腺苷受体阻滞剂）和格列本脲均不能阻断第 1 相弛豫。结论 1) 第 1 相收缩是内皮依赖性的，而第 2 相收缩是内皮非依赖性的； 2) 第 1 相收缩既不依赖于细胞外钙流入，也不依赖于肌浆网的细胞内钙释放，但第 2 相收缩依赖于细胞外 Ca2+ 流入，并且似乎也依赖于蛋白激酶 C 激活； 3) 第 1 相弛豫似乎不是由 EDRF 介导的； 4) PGI2 和 A2 受体结合均不参与第 1 相弛豫，ATP 依赖性 K+ 通道似乎也不参与肺动脉肌缺氧反应。
The response of isolated rat pulmonary arteries to acute hypoxia has previously been reported to be biphasic, consisting of an initial rapid contraction of short duration, followed by partial relaxation (phase 1) and then a second, slowly developed but sustained contraction (phase 2). The purpose of this study was to determine the following: 1) whether products from the endothelium might be required, 2) whether extra- and/or intracellular calcium or protein kinase C might be second messengers in mediating the pulmonary arterial hypoxic contraction, and 3) whether or not guanosine 3',5'-cyclic monophosphate (cGMP), endothelium-derived relaxing factor (EDRF), prostaglandin I2 (PGI2) or A2 adenosine receptor activation is involved in phase 1 relaxation. Neither Ca2+-free media nor verapamil (a Ca2+ channel blocker) altered the phase 1 contraction, but the phase 2 contraction was abolished by either of these treatments. Ryanodine (a sarcoplasmic reticulum Ca2+ depleter) had no effect on phase 1 contraction. H-7 (a PKC inhibitor) inhibited the phase 2 contraction, whereas it had no effect on phase 1 contraction. Removal of the endothelium abolished phase 1 contraction in either Ca2+-free media or normal Ca2+ media but did not alter phase 2 contraction or phase 1 relaxation. Neither methylene blue (guanylate cyclase inhibitor), N(omega)-nitro-L-arginine, (EDRF blocker), acetylsalicylic acid (cyclooxygenase inhibitor), xanthine amino congener (adenosine receptor blocker), nor glybenclamide blocked the phase 1 relaxation. In conclusion 1) phase 1 contraction is endothelium dependent, whereas phase 2 contraction is endothelium independent; 2) phase 1 contraction is neither dependent on extracellular calcum influx nor on intracellular calcium release from the sarcoplasmic reticulum but phase 2 contraction is dependent on extracellular Ca2+ influx and appears to depend upon protein kinase C activation as well; 3) phase 1 relaxation does not appear to be mediated by an EDRF; and 4) neither PGI2 nor A2 receptor binding are involved in the phase 1 relaxation nor do ATP-dependent K+ channels appear to be involved in the pulmonary arterial muscle hypoxic response.