title: [The vasoconstrictor effect of cyclosporine on the pulmonary vein is mediated by its vehicle: the cremophor].
abstract: OBJECTIVE
  Cyclosporin A (CyA) induced vasoconstriction and impaired relaxation to agonists has been related in some models to its vehicle: the cremophor (CRE). There is no data concerning the effect of CyA and its vehicle CRE on the pulmonary veins. Therefore, the present study was designed to characterize the effect of CyA and CRE on isolated pulmonary veins.
  
  
  METHODS
  Third-order canine pulmonary veins (n = 6) were suspended in organ chambers for measurement of isometric force. Segments were exposed to cumulative doses (10(-9) to 10(-4) M) of CyA in its vehicle CRE, and to CRE alone.
  
  
  RESULTS
  CyA induced an ehdothelium-independent vaasoconstriction similar to CRE, maximal constriction (Emax) were: 1.8 +/- 0.3 g versus 2.1 +/- 0.4 g respectively (p = NS). This vasoconstriction observed with CRE was not affected by indomethacine (a cyclooxygenase inhibitor), and by pinane thromboxane (a thromboxane antagonist). However, the vasoconstriction was decreased by diltiazem (10(-5) M), a calcium channel blocker, Emax were: 2.1 +/- 0.4 g and 0.8 +/- 0.04 g respectively for CRE and CRE with diltiazem (p < 0.05).
  
  
  CONCLUSIONS
  CyA vehicle CRE induces an endothelium-independent vasoconstriction in isolated third order pulmonary veins in the dog. This vasoconstriction is not related to a cyclooxygenase product, but is partially mediated by a calcium channel activation in vascular smooth muscle.
authors.affiliation: Service de Chirurgie, Institut de Cardiologie de Montréal, Québec, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Mathieu
authors.forename: P
authors.initials: P
authors.lastname: Demers
authors.forename: S
authors.initials: S
authors.lastname: Elkouri
authors.forename: R
authors.initials: R
authors.lastname: Cartier
mesh_terms: D000818:Animals; D000081008:Bicyclic Monoterpenes; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D014677:Pharmaceutical Vehicles / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011667:Pulmonary Veins / Q000187:drug effects*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000081008:Bicyclic Monoterpenes; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D016861:Cyclooxygenase Inhibitors; D007166:Immunosuppressive Agents; D014677:Pharmaceutical Vehicles; D014665:Vasodilator Agents; C022131:cremophor; D011092:Polyethylene Glycols; D013928:Thromboxane A2; C020465:pinane-thromboxane A2; D016572:Cyclosporine; D004110:Diltiazem; D007213:Indomethacin
vernacular_title: L'effet vasoconstricteur de la cyclosporine sur la veine pulmonaire est médié par son véhicule: le crémophore.