title: Mitochondrial Fission of Smooth Muscle Cells Is Involved in Artery Constriction.
abstract: Mitochondria are dynamic organelles and continuously undergo fission and fusion processes. Mitochondrial fission is involved in multiple physiological or pathological processes, but the role of mitochondrial fission of smooth muscle cells in artery constriction is unknown. The role of mitochondrial fission of smooth muscle cells in arterial function was investigated by measuring the tension of rat mesenteric arteries and thoracic aorta and by evaluating mitochondrial fission, mitochondrial reactive oxygen species, and cytosolic [Ca2+]iin rat vascular smooth muscle cells. Mitochondrial fission inhibitors mdivi-1 and dynasore antagonized phenylephrine- and high K+-induced constriction of rat mesenteric arteries. Mdivi-1 relaxed phenylephrine-induced constriction, and mdivi-1 pretreatment prevented phenylephrine-induced constriction in mice, rat aorta, and human mesenteric arteries. Phenylephrine- and high K+-induced increase of mitochondrial fission in smooth muscle cells of rat aorta and the increase was inhibited by mdivi-1. Mdivi-1 inhibited high K+-induced increases of mitochondrial fission, mitochondrial reactive oxygen species, and cytosolic [Ca2+]iin rat vascular smooth muscle cells. Prechelation of cytosolic Ca2+prevented high K+-induced cytosolic [Ca2+]iincrease, mitochondrial fission, and mitochondrial reactive oxygen species overproduction. Mitochondria-targeted antioxidant mito-TEMPO antagonized phenylephrine- and high K+-induced constriction of rat mesenteric arteries. Nitroglycerin and ROCK (Rho-associated protein kinase) inhibitor Y27632, the 2 vasodilators with different vasorelaxant mechanisms, relaxed high K+-induced vasoconstriction and inhibited high K+-induced mitochondrial fission. In conclusion, the mitochondrial fission of smooth muscle cells is involved in artery constriction.
authors: From the Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics 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.
authors: Ming-Yu
authors: MY
authors: Liu
authors: From the Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics 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.
authors: Jing
authors: J
authors: Jin
authors: From the Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics 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.
authors: Shan-Liang
authors: SL
authors: Li
authors: From the Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics 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.
authors: Jie
authors: J
authors: Yan
authors: From the Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics 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.
authors: Chang-Lin
authors: CL
authors: Zhen
authors: From the Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics 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.
authors: Jin-Lai
authors: JL
authors: Gao
authors: From the Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics 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.
authors: Yong-Hui
authors: YH
authors: Zhang
authors: From the Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics 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.
authors: Yan-Qiu
authors: YQ
authors: Zhang
authors: From the Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics 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.
authors: Xin
authors: X
authors: Shen
authors: From the Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics 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.
authors: Liang-Shuan
authors: LS
authors: Zhang
authors: From the Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics 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.
authors: Yuan-Yuan
authors: YY
authors: Wei
authors: From the Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics 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.
authors: Yu
authors: Y
authors: Zhao
authors: From the Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics 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.
authors: Chen-Guang
authors: CG
authors: Wang
authors: From the Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics 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.
authors: Yun-Long
authors: YL
authors: Bai
authors: From the Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics 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. dongdeli@ems.hrbmu.edu.cn.
authors: De-Li
authors: DL
authors: Dong
mesh_terms: D000577:Amides / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004347:Drug Interactions; D006801:Humans; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000187:drug effects*; D023421:Models, Animal; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D052999:Quinazolinones / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014652:Vascular Diseases / Q000188:drug therapy / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: C549041:3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone; D000577:Amides; D011725:Pyridines; D052999:Quinazolinones; C108830:Y 27632; D010656:Phenylephrine
keywords: arteries; hypertension; mitochondrial dynamics; myocytes, smooth muscle; vasodilation