Cyclosporine-A,but not tacrolimus significantly increases reactivity of vascular smooth muscle cells

Background application of cyclosporine-a (csa) or tacrolimus is associated with numerous side effects. one of the main reasons for restricting usage of csa is hypertension. in tacrolimus treated subjects the frequency of these phenomena is significantly lower. the known molecular mechanism of action of tacrolimus and cyclosporine-a seems to be the same,thus we decided to compare modulatory effect of drugs on vascular smooth muscle contractility. methods experiments were performed on isolated and perfused tail artery of wistar rats. contraction force was measured by increased degree of perfusion pressure with a constant flow rate. results concentration-response curves for agonist in the presence csa were significantly shifted to the left with increase in maximal responses. this effect was due to increased calcium influx from extracellular calcium stores whereas there were no significant changes in calcium influx in the presence of tacrolimus; concentration-response curve was comparable to controls. conclusion our results strongly support the idea that main difference between effects on smooth muscle contractility of calcineurin-dependent immunosuppressants: csa and tacrolimus is related to the different level of extracellular calcium influx to the cytoplasm. the elucidation of these mechanisms may permit the identification of new therapeutic strategies against csa-induced hypertension. © 2015 institute of pharmacology,polish academy of sciences. published by elsevier sp. z o.o. all rights reserved.