EFFECTS OF CYCLOSPORINE-A ON REACTIVITY O F THE RAT AORTA WITH REGENERATED ENDOTHELIUM

Cyclosporine A (CyA) affects vascular reactivity but its effect on loc al vascular tone following endothelial regeneration is unknown. Experi ments were designed to study the effects of CyA on endothelial and smo oth muscle reactivity of endothelium-regenerated arteries. Three group s of rats (n = 8) were subjected to aortic mechanical denudation. Subs equently a first group was treated 8 weeks with CyA (20 mg/kg) and a s econd one with an equivalent volume of CyA vehicle: olive oil (OL). A last group was submitted to a standard diet and repre sented the contr ol group (CTL). After 8 weeks, aortic rings were suspended in organ ch ambers for assessment of endothelial and smooth muscle function. Maxim al 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 +/- 3%, 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). Maxi mal tension to cumulative doses of norepinephrine was increased in rin gs without endothelium treated with CyA (CyA: 5,8 +/- 0,6 g, OL: 4,2 +/- 0,5 g, CTL: 4,0 +/- 0,2g; p < 0,05). All these differences were a bolished in rings studied with endothelium. Endothelial independent re laxation to sodium nitroprusside were similar among all groups. In con clusion, CyA does not specifically affect endothelium-dependent relaxa tion of the regenerated aortic endothelium. However, our model suggest s that CyA increases vascular tone mediated by increased smooth muscle sensitivity to norepinephrine and serotonine but these effects are pr evented by the regenerated endothelium. This experiment demonstrates t he ability of the regenerated endothelium to prevent CyA-induced vascu lar toxicity.