Acute effects of cyclosporin and cremophor EL on endothelial function and vascular smooth muscle in the isolated rat heart.
We studied the effects of cyclosporin dissolved in the vehicle used as an intravenous preparation, namely, cremophor EL, and cremophor alone on the basal coronary flow plus endothelial function and vascular smooth muscle response by examining their influence on 5-hydroxytryptamine (5-HT) and nitroglycerine (GTN) induced the changes in coronary flow in the isolated rat heart. A total of 72 rat hearts were perfused with a modified Langendorf preparation. There was a 12.8 +/- 3% reduction in the basal coronary flow after 60 minutes of perfusion with the drug-free buffer (p = ns). A dose of 50 ng/ml of cremophor or cyclosporin gave a similar reduction in the flow (cremophor 9.2 +/- 0.7%, cyclosporin 12.7 +/- 2%). However, at higher concentrations cremophor caused dose-dependent coronary vasodilation, while cyclosporin had the opposite effect. The maximum effect after 1000 ng/ml of cyclosporin was a 48.7 +/- 0.6% decrease, and after an equivalent dose of cremophor a 24.8 +/- 2.2% increase in the flow. The vasodilatory response to 5-HT and GTN remained unchanged after 60 minutes of perfusion with the drug-free buffer (5-HT, before 33.3 +/- 2.5%, after 37.7 +/- 4.2%; GTN, before 34.3 +/- 2.5%, after 33.7 +/- 1.5%).(ABSTRACT TRUNCATED AT 250 WORDS)
Mankad
P
P
National Heart and Lung Institute, London, UK.
Spatenka
J
J
Slavik
Z
Z
O'Neil
G
G
Chester
A
A
Yacoub
M
M
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects*; D005990:Glycerol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010477:Perfusion; D014677:Pharmaceutical Vehicles; D051381:Rats; D011919:Rats, Inbred Strains
D014677:Pharmaceutical Vehicles; C000515:cremophor EL; D016572:Cyclosporine; D005990:Glycerol