title: Direct vascular effects in the rat of the vehicles used for the intravenous and oral administration of cyclosporin A.
abstract: 1. The contraction and relaxation responses to the polyoxyethylated vehicles currently used for the intravenous and oral administration of cyclosporin A in allograft recipients were studied in isolated rat aorta. The results were compared with those obtained with commercially available cyclosporin A for intravenous administration. 2. None of these compounds affected resting tension, noradrenaline-induced contraction or endothelium-independent relaxation produced by sodium nitroprusside or bumetanide. However, they all reversed the relaxation induced by acetylcholine, carbamylcholine or adenosine 5'-triphosphate, by a factor of approximately 66%. 3. This reversal of relaxation was unaffected by indomethacin and did not require the presence of cyclosporin A in the vehicles, and was completely abolished by L-arginine (3 x 10(-5) mol/l). 4. It is concluded that vehicles used for commercial preparations of cyclosporin A interfere with the synthesis of endothelium-derived relaxing factor at an early stage during which L-arginine is made available for enzymatic degradation.
authors.affiliation: Instituto de Investigaciones Cardiológicas, Facultad de Medicina, Buenos Aires, Argentina.
authors.forename: C
authors.initials: C
authors.lastname: Amorena
authors.forename: A
authors.initials: A
authors.lastname: Castro
authors.forename: A
authors.initials: A
authors.lastname: Müller
authors.forename: M F
authors.initials: MF
authors.lastname: Villamil
mesh_terms: D000284:Administration, Oral; D000818:Animals; D046508:Culture Techniques; D003524:Cyclosporins / Q000008:administration & dosage* / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D003524:Cyclosporins; C022131:cremophor; D011092:Polyethylene Glycols