Tacrolimus inhibits vasoconstriction by increasing Ca2+ sparks in rat aorta

• DOI: 10.1007/s11596-016-1534-6
• Publication Date: 2016-02-02T05:49:38Z
• Authors: Yu-fang Chen; Chen Wang; Rui Zhang; Huan Wang; Rong Ma; Si Jin; Ji-zhou Xiang; Qiang Tang
• Keywords: Male; 0303 health sciences; Ryanodine; Myocytes, Smooth Muscle; Muscle, Smooth, Vascular; Tacrolimus; Rats; 3. Good health; Rats, Sprague-Dawley; Norepinephrine; 03 medical and health sciences; Vasoconstriction; Animals; Calcium Signaling; Large-Conductance Calcium-Activated Potassium Channels; Aorta; Cells, Cultured

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.