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The Ca<jats:sup>2+<\/jats:sup>entering from outside into the cell triggers Ca<jats:sup>2+<\/jats:sup>release from the sarcoplasmic reticulum (<jats:styled-content style=\"fixed-case\">SR<\/jats:styled-content>) stores. To refill the depleted Ca<jats:sup>2+<\/jats:sup>stores in the<jats:styled-content style=\"fixed-case\">SR<\/jats:styled-content>, another type of Ca<jats:sup>2+<\/jats:sup>channels in the cell membrane, known as store\u2010operated Ca<jats:sup>2+<\/jats:sup>channels (<jats:styled-content style=\"fixed-case\">SOCC<\/jats:styled-content>), are activated. These<jats:styled-content style=\"fixed-case\">SOCC<\/jats:styled-content>s are verapamil and nifedipine resistant, but are<jats:styled-content style=\"fixed-case\">SKF<\/jats:styled-content>96465 (<jats:styled-content style=\"fixed-case\">SK<\/jats:styled-content>) and gadolinium (Gd<jats:sup>3+<\/jats:sup>) sensitive. Both<jats:styled-content style=\"fixed-case\">SK<\/jats:styled-content>and Gd<jats:sup>3+<\/jats:sup>have been shown to reduce [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>in the smooth muscle, but their effects on blood pressure have not been reported. Our results demonstrated that both<jats:styled-content style=\"fixed-case\">SK<\/jats:styled-content>and Gd<jats:sup>3+<\/jats:sup>produced a dose\u2010dependent reduction in blood pressure in rat. The combination of<jats:styled-content style=\"fixed-case\">SK<\/jats:styled-content>and verapamil produced an additive action in lowering the blood pressure. Furthermore,<jats:styled-content style=\"fixed-case\">SK<\/jats:styled-content>, but not Gd<jats:sup>3+<\/jats:sup>suppressed proliferation of vascular smooth muscle cells in the absence or presence of lysophosphatidic acid (<jats:styled-content style=\"fixed-case\">LPA<\/jats:styled-content>).<jats:styled-content style=\"fixed-case\">SK<\/jats:styled-content>decreased the elevation of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>induced by<jats:styled-content style=\"fixed-case\">LPA<\/jats:styled-content>, endothelin\u20101 (<jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101) and angiotensin II (Ang II), but did not affect the norepinephrine (<jats:styled-content style=\"fixed-case\">NE<\/jats:styled-content>)\u2010evoked increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. On the other hand, Gd<jats:sup>3+<\/jats:sup>inhibited the<jats:styled-content style=\"fixed-case\">LPA<\/jats:styled-content>and Ang II induced change in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>, but had no effect on the<jats:styled-content style=\"fixed-case\">ET<\/jats:styled-content>\u20101 and<jats:styled-content style=\"fixed-case\">NE<\/jats:styled-content>induced increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. The combination of verapamil and<jats:styled-content style=\"fixed-case\">SK<\/jats:styled-content>abolished the<jats:styled-content style=\"fixed-case\">LPA<\/jats:styled-content>\u2010 or adenosine\u20105\u2032\u2010triphosphate (ATP)\u2010induced [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>augmentation. These results suggest that<jats:styled-content style=\"fixed-case\">SOCC<\/jats:styled-content>inhibitors, like<jats:styled-content style=\"fixed-case\">VOCC<\/jats:styled-content>blocker, may serve as promising drugs for the treatment of hypertension.<\/jats:p>","DOI":"10.1111\/jcmm.12684","type":"journal-article","created":{"date-parts":[[2015,10,16]],"date-time":"2015-10-16T07:04:44Z","timestamp":1444979084000},"page":"2763-2770","source":"Crossref","is-referenced-by-count":17,"title":["Reduction of blood pressure by store\u2010operated calcium channel blockers"],"prefix":"10.1111","volume":"19","author":[{"given":"Yan\u2010Jun","family":"Xu","sequence":"first","affiliation":[{"name":"Institute of Cardiovascular Sciences St. Boniface Hospital Research Centre Department of Physiology and Pathophysiology Faculty of Health Sciences University of Manitoba Winnipeg MB 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