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 si de effects including hypertension. Here, we investigated the effects of CsA on intracellular free calcium ([Ca2+](i)) and the mechanisms involved in v asoconstriction in cultured human coronary myocytes. We used the Fura-2 tec hnique for Ca2+ imaging. Acute application of CsA at therapeutic concentrat ions (0.1-10 mu mol/l) had no effect. Chronic exposure to CsA (1 mu mol/l) for 24 h induced a small (20 nmol/l) but highly significant increase of bas al [Ca2+](i) and enhanced the occurrence of spontaneous Ca2+ oscillations. Endothelin- and vasopressin-induced rises of [Ca2+](i) were also enhanced. The demonstration that CsA increases basal [Ca2+](i) in addition to its imp act on agonist receptor stimulation is of major importance for new therapeu tic approaches. (C) 2001 Published by Elsevier Science B.V. on behalf of th e Federation of European Biochemical Societies.