title: Cyclosporine-A, but not tacrolimus significantly increases reactivity of vascular smooth muscle cells.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland. Electronic address: ellag@cm.umk.pl.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Grześk
authors.affiliation: Department of Pharmacology and Therapeutics, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Malinowski
authors.affiliation: Department of Pharmacology and Therapeutics, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Wiciński
authors.affiliation: Department of Pharmacology and Therapeutics, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Szadujkis-Szadurska
authors.affiliation: Department of Pharmacology and Therapeutics, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Thabit A
authors.initials: TA
authors.lastname: Sinjab
authors.affiliation: Department of Laboratory Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Manysiak
authors.affiliation: Department of Pediatrics, Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Tejza
authors.affiliation: Department of Liver and General Surgery, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Słupski
authors.affiliation: Department of Laboratory Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Grażyna
authors.initials: G
authors.lastname: Odrowąż-Sypniewska
authors.affiliation: Department of Pharmacology and Therapeutics, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Grześk
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
chemical_list: D016572:Cyclosporine; D002118:Calcium; D016559:Tacrolimus
keywords: Cyclosporine A; Hypertension; Smooth muscle reactivity; Tacrolimus