Dagenais F, Hollmann C, Buluran J, Cartier R
Département de Chirurgie, Institut de Cardiologie de Montréal, Québec, Canada.
Ann Chir. 1995;49(8):694-9.
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.
环孢素A（CyA）会影响血管反应性，但其对内皮再生后局部血管张力的影响尚不清楚。本实验旨在研究CyA对内皮再生动脉的内皮和平滑肌反应性的影响。将三组大鼠（每组n = 8）进行主动脉机械剥脱术。随后，第一组用CyA（20mg/kg）治疗8周，第二组用等量的CyA溶媒：橄榄油（OL）治疗。最后一组给予标准饮食，作为对照组（CTL）。8周后，将主动脉环悬挂在器官浴槽中评估内皮和平滑肌功能。对乙酰胆碱的最大内皮依赖性舒张（CyA组：52±3%，OL组：50±4%，CTL组：48±5%；p = 无显著性差异）、二磷酸腺苷（CyA组：30±7%，OL组：18±2%，CTL组：24±5%；p = 无显著性差异）和组胺（CyA组：38±6%，OL组：43±4%，CTL组：47±5%；p = 无显著性差异）在所有组之间相当。在无内皮的主动脉节段研究中，OL组对血清素的收缩增加显著减轻（CyA组：259±43%，OL组：153±11%，CTL组：243±24%；p < 0.05）。用CyA处理的无内皮环中，对去甲肾上腺素累积剂量的最大张力增加（CyA组：5.8±0.6g，OL组：4.2±0.5g，CTL组：4.0±0.2g；p < 0.05）。在用内皮研究的环中，所有这些差异均消失。对硝普钠的非内皮依赖性舒张在所有组之间相似。总之，CyA不会特异性影响再生主动脉内皮的内皮依赖性舒张。然而，我们的模型表明，CyA通过增加平滑肌对去甲肾上腺素和血清素的敏感性来增加血管张力，但这些作用被再生内皮所阻止。本实验证明了再生内皮预防CyA诱导的血管毒性的能力。
