期刊
HYPERTENSION
卷 61, 期 1, 页码 137-+出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.112.197863
关键词
calcium channel; alpha(1C) subunit; beta 3 subunit; hypertension; mesenteric arteries
资金
- National Institutes of Health [R01 HL064806-12]
- South Central Affiliate of the American Heart Association [092250224]
Voltage-gated L-type Ca2+ (Ca(v)1.2) channels in vascular smooth muscle cells are a predominant Ca2+ influx pathway that mediates arterial tone. Channel biogenesis is accomplished when the pore-forming alpha(1C) subunit coassembles with regulatory Ca-v beta subunits intracellularly, and the multiprotein Ca(v)1.2 channel complex translocates to the plasma membrane to form functional Ca2+ channels. We hypothesized that the main Ca-v beta isoform in vascular smooth muscle cells, Ca-v beta 3, is required for the upregulation of arterial Ca(v)1.2 channels during the development of hypertension, an event associated with abnormal Ca2+-dependent tone. Ca(v)1.2 channel expression and function were compared between second-order mesenteric arteries of C57BL/6 wild-type (WT) and Ca-v beta 3(-/-) mice infused with saline (control) or angiotensin II (Ang II) for 2 weeks to induce hypertension. The mesenteric arteries of Ang II-infused WT mice showed increased Ca(v)1.2 channel expression and accentuated Ca2+-mediated contractions compared with saline-infused WT mice. In contrast, Ca(v)1.2 channels failed to upregulate in mesenteric arteries of Ang II-infused Ca-v beta 3(-/-) mice, and Ca2+-dependent reactivity was normal in these arteries. Basal systolic blood pressure was not significantly different between WT and Ca-v beta 3(-/-) mice (98 +/- 2 and 102 +/- 3 mm Hg, respectively), but the Ca-v beta 3(-/-) mice showed a blunted pressor response to Ang II infusion. Two weeks after the start of Ang II administration, the systolic blood pressure of Ca-v beta 3(-/-) mice averaged 149 +/- 4 mm Hg compared with 180 +/- 5 mm Hg in WT mice. Thus, the Ca-v beta 3 subunit is a critical regulatory protein required to upregulate arterial Ca(v)1.2 channels and fully develop Ang II-dependent hypertension in C57BL/6 mice. (Hypertension. 2013;61:137-142.). circle Online Data Supplement
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