Vasorelaxation and inhibition of the voltage‐operated Ca2+ channels by FK506 in the porcine coronary artery

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Abstract
Using fura‐2 fluorometry, the effects of FK506, an immunosuppressant, on changes in cytosolic Ca2+ concentrations ([Ca2+]i) and tension were investigated in porcine coronary arterial strips. The effects of FK506 on the activity of voltage‐operated Ca2+ channels were examined by applying a whole cell patch clamp to the isolated smooth muscle cells of porcine coronary artery. FK506 inhibited the sustained increases in both [Ca2+]i and tension induced by 118 mM K+ depolarization and 100 nM U46619 in a concentration‐dependent manner (1–30 μM). The extent of inhibition of the K+‐induced contraction was greater than that of the U46619‐induced contraction. The increases in [Ca2+]i and tension induced by histamine and endothelin‐1 in the presence of extracellular Ca2+ were also inhibited by 10 μM FK506. FK506 (10 μM) had no effect on Ca2+ release induced by caffeine or by histamine in the Ca2+‐free solution. FK506 (10 μM) had no effect on the [Ca2+]i‐tension relationships of the contractions induced by cumulative increases of extracellular Ca2+ during K+ depolarization or stimulation with U46619. In the patch clamp experiments, FK506 (30 μM) partially inhibited the inward current induced by depolarization pulse from −80 mV to 0 mV. In conclusion, FK506 induces arterial relaxation by decreasing [Ca2+]i mainly due to the inhibition of the L‐type Ca2+ channels, with no effect on the Ca2+ sensitivity of the contractile apparatus. British Journal of Pharmacology (1999) 126, 717–729; doi:10.1038/sj.bjp.0702339