Hypoxic vasorelaxation inhibition by organ culture correlates with loss of Kv channels but not Ca(2+) channels.
Hypoxic vasorelaxation inhibition by organ culture correlates with loss of Kv channels but not Ca(2+) channels.
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器官培养引起的缺氧血管舒张抑制与 Kv 通道的丧失相关，但与 Ca(2 ) 通道的丧失无关。
DOI：
10.1152/ajpheart.00569.2001
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Paul,RichardJ
中科院分区：
文献类型：
--
作者：
Thorne,GeorgeD;Conforti,Laura;Paul,RichardJ
我们（Thorne GD，Shimizu S，and Paul RJ.Am J Physiol Cell Physiol 281：C24-C32，2001）最近已经表明，器官培养24小时特异性地抑制猪冠状动脉对急性缺氧（95%N2 - 5%CO2）的舒张。在这里，我们在猪颈动脉和大鼠和小鼠主动脉中显示了类似的结果。在冠状动脉中，器官培养后不能松弛至缺氧的部分原因与缺氧期间降低细胞内Ca 2+浓度（[Ca 2 +]i）的能力的伴随损失有关（Thorne GD，Shimizu S，and Paul RJ.Am J Physiol Cell Physiol 281：C24-C32，2001）。为了阐明缺氧导致舒张功能丧失的机制，我们研究了在血管平滑肌（VSM）[Ca 2 +]失调中起关键作用的K+和Ca 2+通道活性和基因表达的变化。逆转录聚合酶链反应显示大鼠主动脉O2敏感性K+通道（Kv1.5和Kv2.1）的mRNA表达减少。与此相反，在其他表达的电压门控性K+通道（Kv1.2和Kv1.3）或Ca 2+通道亚型的变化被发现。修改的K+通道的表达支持的功能证据表明，减少响应一般K+通道激活，吡那地尔，和特定的电压依赖性K+（Kv）通道阻断4-氨基吡啶。总之，器官培养降低了特异性Kv通道的表达。这些变化与VSM收缩性的改变机制一致，可能参与缺氧诱导的血管舒张的Ca 2+依赖性途径。
We (Thorne GD, Shimizu S, and Paul RJ.Am J Physiol Cell Physiol281: C24–C32, 2001) have recently shown that organ culture for 24 h specifically inhibits relaxation to acute hypoxia (95% N2-5% CO2) in the porcine coronary artery. Here we show similar results in the porcine carotid artery and the rat and mouse aorta. In the coronary artery, part of the inability to relax to hypoxia after organ culture is associated with a concomitant loss in ability to reduce intracellular Ca2+concentration ([Ca2+]i) during hypoxia (Thorne GD, Shimizu S, and Paul RJ.Am J Physiol Cell Physiol281: C24–C32, 2001). To elucidate the mechanisms responsible for the loss of relaxation to hypoxia, we investigated changes in K+and Ca2+channel activity and gene expression that play key roles in [Ca2+]iregulation in vascular smooth muscle (VSM). Reduced mRNA expression of O2-sensitive K+channels (Kv1.5 and Kv2.1) was shown by reverse transcriptase-polymerase chain reaction in the rat aorta. In contrast, no change in other expressed voltage-gated K+channels (Kv1.2 and Kv1.3) or Ca2+channel subtypes was found. Modified K+channel expression is supported by functional evidence indicating a reduced response to general K+channel activation, by pinacidil, and to specific voltage-dependent K+(Kv) channel blockade by 4-aminopyridine. In conclusion, organ culture decreases expression of specific Kv channels. These changes are consistent with altered mechanisms of VSM contractility that may be involved in Ca2+-dependent pathways of hypoxia-induced vasodilation.
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影响因子：
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作者：
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