[Effects of cyclosporine A on the reactivity of the aorta with regenerated endothelium in rats].
Cyclosporine A (CyA) affects vascular reactivity but its effect on local vascular tone following endothelial regeneration is unknown. Experiments were designed to study the effects of CyA on endothelial and smooth muscle reactivity of endothelium-regenerated arteries. Three groups of rats (n = 8) were subjected to aortic mechanical denudation. Subsequently a first group was treated 8 weeks with CyA (20 mg/kg) and a second one with an equivalent volume of CyA vehicle: olive oil (OL). A last group was submitted to a standard diet and represented the control group (CTL). After 8 weeks, aortic rings were suspended in organ chambers for assessment of endothelial and smooth muscle function. Maximal endothelial dependent relaxation to acetylcholine (CyA: 52 +/- 3%, OL: 50 +/- 4%, CTL: 48 +/- 5%; p = NS), adenosine diphosphate (CyA: 30 +/- 7%, OL: 18 +/- 2%, CTL: 24 +/- 5%; p = NS) and histamine (CyA: 38 +/- 6%, OL: 43 +/- 4%, CTL: 47 +/- 5%; p = NS) were comparable among all groups. In aortic segments studies without endothelium, increased contraction to serotonine was significantly lessened in the OL group (CyA: 259 +/- 43%, OL: 153 +/- 11%, CTL: 243 +/- 24%; p < 0.05). Maximal tension to cumulative doses of norepinephrine was increased in rings without endothelium treated with CyA (CyA: 5.8 +/- 0.6 g, OL: 4.2 +/- 0.5 g, CTL: 4.0 +/- 0.2 g; p < 0.05). All these differences were abolished in rings studied with endothelium. Endothelial independent relaxation to sodium nitroprusside were similar among all groups. In conclusion, CyA does not specifically affect endothelium-dependent relaxation of the regenerated aortic endothelium. However, our model suggests that CyA increases vascular tone mediated by increased smooth muscle sensitivity to norepinephrine and serotonine but these effects are prevented by the regenerated endothelium. This experiment demonstrates the ability of the regenerated endothelium to prevent CyA-induced vascular toxicity.
Dagenais
F
F
Département de Chirurgie, Institut de Cardiologie de Montréal, Québec, Canada.
Hollmann
C
C
Buluran
J
J
Cartier
R
R
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D007166:Immunosuppressive Agents; D017366:Serotonin Receptor Agonists; D014662:Vasoconstrictor Agents; D012701:Serotonin; D016572:Cyclosporine; D009638:Norepinephrine
Les effets de la cyclosporine A sur la réactivité de l'aorte de rat avec endothélium régénéré.