The ouabain-binding site of the α2 isoform of Na,K-ATPase plays a role in blood pressure regulation during pregnancy.
The ouabain-binding site of the α2 isoform of Na,K-ATPase plays a role in blood pressure regulation during pregnancy.
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Na,K-ATP酶α2亚型的哇巴因结合位点在妊娠期间的血压调节中发挥作用。
DOI：
10.1038/ajh.2010.195
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发表时间：
2010
影响因子：
3.2
通讯作者：
Lingrel,JerryB
中科院分区：
文献类型：
--
作者：
Oshiro,Naomi;Dostanic-Larson,Iva;Neumann,JonC;Lingrel,JerryB
背景Na，K-ATP酶α亚基的强心甾体/哇巴因结合位点被认为在心血管稳态中起重要作用。以前，我们使用基因修饰的α 2 R/R小鼠证明了α2Na，K-ATP酶的强心类固醇结合位点参与促肾上腺皮质激素（ACTH）诱导的高血压，与哇巴因敏感的野生型α2S/S小鼠相比，强心类固醇结合位点对哇巴因相对耐药。为了进一步探讨该位点在心血管系统中的重要性，我们研究了α 2 R/Risoform对妊娠期小鼠血压的调节作用。结果α 2 S/S小鼠在妊娠前2个月收缩压逐渐下降，妊娠晚期收缩压逐渐升高，高于受孕前水平，妊娠第7天和第17天收缩压下降，妊娠第17天收缩压下降。然而，α 2 R/R小鼠在妊娠晚期表现出较低的血压。在整个妊娠期，α2S/S小鼠心肌α2Na，K-ATP酶的表达明显低于α 2 R/R小鼠。结论α 2 Na，K-ATP酶强心甾体结合位点在维持妊娠期正常收缩压中起重要作用。
BackgroundThe cardiotonic steroid/ouabain-binding site of the α subunit of Na,K-ATPase is thought to play an important role in cardiovascular homeostasis. Previously, we demonstrated the cardiotonic steroid–binding site of the α2Na,K-ATPase is involved in adrenocorticotropic hormone (ACTH)–induced hypertension by using gene-modified α2R/Rmice in which the cardiotonic steroid–binding site is relatively resistant to ouabain compared to the ouabain-sensitive wild-type α2S/Smice. To further explore the importance of this site in the cardiovascular system, we investigated blood pressure regulation during pregnancy in mice with the α2R/Risoform.MethodsThe systolic blood pressure (SBP) of the α2S/Sand α2R/Rmice was measured before and during pregnancy by tail-cuff. The expression of the α isoforms of Na, K-ATPase in various tissues and plasma endogenous ouabain contents were assessed prior to pregnancy as well as days 7 and 17 of gestation.ResultsThe α2S/Smice showed a gradual decrease in the SBP during the first two trimesters, followed by an increase above the preconceptional level in the third trimester. However, the α2R/Rmice exhibited a lower blood pressure in the third trimester. The cardiac expression of the α2Na,K-ATPase in the α2S/Smice was significantly less than that of the α2R/Rmice throughout the pregnancy. The plasma endogenous ouabain concentration significantly increased by twofold at day 17 of pregnancy in the α2R/Rmice but not in the α2S/Smice.ConclusionsThe cardiotonic steroid–binding site of the α2Na,K-ATPase plays a role in maintaining normal SBP during pregnancy.