The β3 subunit contributes to vascular calcium channel upregulation and hypertension in angiotensin II-infused C57BL/6 mice.
The β3 subunit contributes to vascular calcium channel upregulation and hypertension in angiotensin II-infused C57BL/6 mice.
复制标题
β3亚基有助于血管钙通道上调和血管紧张素II注入的C57BL/6小鼠的高血压。
DOI：
10.1161/hypertensionaha.112.197863
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发表时间：
2013-01
期刊：
影响因子：
--
通讯作者：
Rusch NJ
中科院分区：
文献类型：
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作者：
Kharade SV;Sonkusare SK;Srivastava AK;Thakali KM;Fletcher TW;Rhee SW;Rusch NJ
Voltage-gated L-type Ca2+ (Cav1.2) channels in vascular smooth muscle cells (VSMCs) are a predominant Ca2+ influx pathway that mediates arterial tone. Channel biogenesis is accomplished when the pore-forming α1C subunit co-assembles with regulatory Cavβ subunits intracellularly, and the multi-protein Cav1.2 complex translocates to the plasma membrane to form functional Ca2+ channels. We hypothesized that the main Cavβ isoform in VSMCs, Cavβ3, is required for the upregulation of arterial Cav1.2 channels during the development of hypertension, an event associated with abnormal Ca2+-dependent tone. Cav1.2 channel expression and function was compared between 2nd order mesenteric arteries (MA) of C57BL/6 wild-type (WT) and Cavβ3-/- mice infused with saline (control) or angiotensin II (Ang II) for 2 weeks to induce hypertension. The MA of Ang II-infused WT mice showed increased Cav1.2 channel expression and accentuated Ca2+-mediated contractions compared to saline-infused WT mice. In contrast, Cav1.2 channels failed to upregulate in MA of Ang II-infused Cavβ3-/- mice and Ca2+-dependent reactivity was normal in these arteries. Basal systolic blood pressure (SBP) was not significantly different between WT and Cavβ3-/- mice (98±2 mm Hg and 102±3 mm Hg, respectively), but the Cavβ3-/- mice showed a blunted pressor response to Ang II infusion. Two weeks after the start of Ang II administration, the SBP of Cavβ3-/- mice averaged 149±4 mm Hg compared to 180±5 mm Hg in WT mice. Thus, the Cavβ3 subunit is a critical regulatory protein required to upregulate arterial Cav1.2 channels and fully develop angiotensin II –dependent hypertension in C57BL/6 mice.
