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 micromol/l) had no effect. Chronic exposure to CsA (1 micromol/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.
Frapier
J M
JM
Service de Chirurgie Cardiothoracique, INSERM U-390, Hôpital Arnaud de Villeneuve, Montpellier, France.
Choby
C
C
Mangoni
M E
ME
Nargeot
J
J
Albat
B
B
Richard
S
S
D000293:Adolescent; D000328:Adult; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000494:pharmacology; D016257:Fura-2 / Q000494:pharmacology; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013997:Time Factors; D014667:Vasopressins / Q000378:metabolism*
D016232:Endothelins; D005456:Fluorescent Dyes; D007166:Immunosuppressive Agents; D014667:Vasopressins; D016572:Cyclosporine; D002118:Calcium; D016257:Fura-2