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Here, we characterized the effects of the typical mitochondrial uncoupler carbonyl cyanide m\u2010chlorophenylhydrazone (CCCP) on vascular function in rat mesenteric arteries and aorta and elucidated the potential mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Isometric tension of mesenteric artery and thoracic aorta was recorded by using a multiwire myograph system. Protein levels were measured by western blot analyses. Cytosolic [Ca<jats:sup>2<\/jats:sup><jats:sup>+<\/jats:sup>]<jats:sub>i<\/jats:sub>, mitochondrial ROS (mitoROS) and mitochondrial membrane potential of smooth muscle cells (A10) were measured by laser scanning confocal microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Acute treatment with CCCP relaxed phenylephrine (PE)\u2010 and high K<jats:sup>+<\/jats:sup>(KPSS)\u2010induced constriction of rat mesenteric arteries with intact and denuded endothelium. Pretreatment with CCCP prevented PE\u2010 and KPSS\u2010induced constriction of rat mesenteric arteries with intact and denuded endothelium. Similarly, CCCP prevented PE\u2010 and KPSS\u2010induced constriction of rat thoracic aorta. CCCP increased the cellular ADP\/ATP ratio in vascular smooth muscle cells (A10) and activated AMPK in A10 cells and rat thoracic aorta tissues. CCCP\u2010induced aorta relaxation was attenuated in AMPK \u03b11 knockout (\u2212\/\u2212) mice. SERCA inhibitors thapsigargin and cyclopiazonic acid (CPA) but not the K<jats:sub>ATP<\/jats:sub>channel blocker glibenclamide partially inhibited CCCP\u2010induced vasorelaxation in endothelium\u2010denuded rat mesenteric arteries. CCCP increased cytosolic [Ca<jats:sup>2<\/jats:sup><jats:sup>+<\/jats:sup>]<jats:sub>i<\/jats:sub>, mitoROS production and depolarized mitochondrial membrane potential in A10 cells. FCCP, the analogue of CCCP, had similar vasoactivity as CCCP in rat mesenteric arteries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>CCCP induces vasorelaxation by a mechanism that does not involve K<jats:sub>ATP<\/jats:sub>channel activation in smooth muscle cells of arteries.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13578","type":"journal-article","created":{"date-parts":[[2016,8,18]],"date-time":"2016-08-18T06:12:40Z","timestamp":1471500760000},"page":"3145-3158","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Mitochondrial uncoupler carbonyl cyanide m\u2010chlorophenylhydrazone induces vasorelaxation without involving K<sub>ATP<\/sub>channel activation in smooth muscle cells of arteries"],"prefix":"10.1111","volume":"173","author":[{"given":"Yan\u2010Qiu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences Harbin Medical University Harbin PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences Harbin Medical University Harbin PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Lin","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the 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