title: Tacrolimus inhibits vasoconstriction by increasing Ca(2+) sparks in rat aorta.
abstract: The present study attempted to test a novel hypothesis that Ca(2+) sparks play an important role in arterial relaxation induced by tacrolimus. Recorded with confocal laser scanning microscopy, tacrolimus (10 µmol/L) increased the frequency of Ca(2+) sparks, which could be reversed by ryanodine (10 µmol/L). Electrophysiological experiments revealed that tacrolimus (10 µmol/L) increased the large-conductance Ca(2+)-activated K(+) currents (BKCa) in rat aortic vascular smooth muscle cells (AVSMCs), which could be blocked by ryanodine (10 µmol/L). Furthermore, tacrolimus (10 and 50 µmol/L) reduced the contractile force induced by norepinephrine (NE) or KCl in aortic vascular smooth muscle in a concentration-dependent manner, which could be also significantly attenuated by iberiotoxin (100 nmol/L) and ryanodine (10 µmol/L) respectively. In conclusion, tacrolimus could indirectly activate BKCa currents by increasing Ca(2+) sparks released from ryanodine receptors, which inhibited the NE- or KCl-induced contraction in rat aorta.
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Yu-Fang
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Ma
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Si
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Ji-Zhou
authors.initials: JZ
authors.lastname: Xiang
authors.affiliation: Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. tangqiang_tjmu@hust.edu.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tang
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D020013:Calcium Signaling; D002478:Cells, Cultured; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology*; D014661:Vasoconstriction
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D012433:Ryanodine; D016559:Tacrolimus; D009638:Norepinephrine
keywords: Ca2+ sparks; large-conductance Ca2+-activated K+ channels; tacrolimus; vasoconstriction
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