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Tacrolimus inhibits vasoconstriction by increasing Ca(2+) sparks in rat aorta / 华中科技大学学报(医学)(英德文版)
Journal of Huazhong University of Science and Technology (Medical Sciences) ; (6): 8-13, 2016.
Article in English | WPRIM | ID: wpr-250314
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.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Aorta / Pharmacology / Physiology / Ryanodine / Vasoconstriction / Norepinephrine / Cells, Cultured / Tacrolimus / Rats, Sprague-Dawley / Calcium Signaling Limits: Animals Language: English Journal: Journal of Huazhong University of Science and Technology (Medical Sciences) Year: 2016 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Aorta / Pharmacology / Physiology / Ryanodine / Vasoconstriction / Norepinephrine / Cells, Cultured / Tacrolimus / Rats, Sprague-Dawley / Calcium Signaling Limits: Animals Language: English Journal: Journal of Huazhong University of Science and Technology (Medical Sciences) Year: 2016 Type: Article