Ciclosporin A inhibits endothelium-dependent vasodilatation and vascular prostacyclin production.
Aortic rings dissected from rats treated with ciclosporin A (30 mg/kg per day for five days) showed reduced relaxation induced by the endothelium-dependent vasodilator acetylcholine, but unchanged responses induced by glyceryl trinitrate. After eight weeks of ciclosporin A treatment, the relaxation induced by both acetylcholine and glyceryl trinitrate was inhibited. In addition, phenylephrine-induced contractions were slightly enhanced and vascular prostacyclin production was reduced by more than 80%. These effects may participate in the hypertensive and thrombo-embolic complications associated with the clinical use of ciclosporin A.
Bossaller
C
C
Department of Cardiology, German Heart Institute Berlin.
Förstermann
U
U
Hertel
R
R
Olbricht
C
C
Reschke
V
V
Fleck
E
E
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D003524:Cyclosporins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D011464:Epoprostenol / Q000096:biosynthesis*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects*
D003524:Cyclosporins; D010656:Phenylephrine; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D000109:Acetylcholine