Potentiation of vascular smooth muscle cell activity by cyclosporin A.
Pretreatment of rat vascular smooth muscle cells with cyclosporin A caused concentration- and time-dependent enhancement of both angiotensin II- and platelet-derived growth factor-stimulated cellular functions, which may be related to a rise in vascular tone. In particular, cyclosporin A increased cytosolic free calcium, and augmented the agonist-induced formation of inositol polyphosphate. In addition, it markedly increased the sensitivity of the cells to platelet-derived growth factor-mediated stimulation of thymidine incorporation. The potentiation of vascular smooth muscle cell activity by cyclosporin A may be a novel mechanism by which it exerts an adverse vasoconstrictor effect.
Locher
R
R
Department of Internal Medicine, University Hospital, Zürich, Switzerland.
Huss
R
R
Vetter
W
W
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D007295:Inositol Phosphates / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D013936:Thymidine / Q000378:metabolism
D007295:Inositol Phosphates; D010982:Platelet-Derived Growth Factor; D000804:Angiotensin II; D016572:Cyclosporine; D004247:DNA; D002118:Calcium; D013936:Thymidine