Cyclosporin A increases basal intracellular calcium and calcium responses to endothelin and vasopressin in human coronary myocytes

Cyclosporin A (CsA) is a widely used immunosuppressive agent with severe side effects including hypertension. Here, we investigated the effects of CsA on intracellular free calcium ([Ca 2+] i) and the mechanisms involved in vasoconstriction in cultured human coronary myocytes. We used the Fura-2 technique for Ca 2+ imaging. Acute application of CsA at therapeutic concentrations (0.1–10 μmol/l) had no effect. Chronic exposure to CsA (1 μmol/l) for 24 h induced a small (20 nmol/l) but highly significant increase of basal [Ca 2+] i and enhanced the occurrence of spontaneous Ca 2+ oscillations. Endothelin- and vasopressin-induced rises of [Ca 2+] i were also enhanced. The demonstration that CsA increases basal [Ca 2+] i in addition to its impact on agonist receptor stimulation is of major importance for new therapeutic approaches.