Latulippe J F, Buluran J, Cartier R
Département de Chirurgie, Institut de Cardiologie de Montréal, Québec, Canada.
Ann Chir. 1995;49(8):712-8.
Chronic administration of cyclosporine (CyA) has been shown to affect local vascular tone. Pentoxifylline (PTX), a xanthine-derived vasoactive agent, has been reported to prevent CyA toxicity but its effect on CyA-related increased vascular tone remains uncertain. In vitro experiments were designed to study the effects of PTX on endothelium-dependent and independent vasorelaxation of the rat thoracic aorta. Three groups of rats (n = 10) were respectively treated for 4 weeks with CyA (30 mg/kg/day), CyA and PTX (40 mg/kg/day), and CyA and PTX (80 mg/kg/day). At the end of the period, rings (4-5 mm) of aorta were harvested and suspended in organ chambers containing Krebs Ringer solution (37 degrees C, 95% O2, 5% CO2) for assessment of endothelial and smooth muscle reactivity. Endothelium-dependent relaxation to acetylcholine was significantly enhanced in animals treated with CyA and PTX (40 mg/kg/day) compared to those exposed to CyA alone (p < 0.05). Response to histamine and adenosine diphosphate was not affected. However, the use of PTX (80 mg/kg/day) significantly deteriorated the endothelial response to the same drugs (p < 0.05) suggesting a detrimental effect of PTX at this concentration. Endothelial-independent relaxation to sodium nitroprusside was comparable in all groups. The results suggest the clinical benefit reported with the use of PTX on patients chronically exposed to CyA may partly be due to an improvement of the vascular endothelial function. However, the toxicity encountered at high dose should cautioned its use in clinical setup.
长期给予环孢素（CyA）已被证明会影响局部血管张力。己酮可可碱（PTX）是一种黄嘌呤衍生的血管活性药物，据报道可预防CyA毒性，但其对CyA相关血管张力增加的影响仍不确定。本研究设计了体外实验，以研究PTX对大鼠胸主动脉内皮依赖性和非内皮依赖性血管舒张的影响。将三组大鼠（每组n = 10）分别用CyA（30 mg/kg/天）、CyA和PTX（40 mg/kg/天）以及CyA和PTX（80 mg/kg/天）治疗4周。在实验周期结束时，采集主动脉环（4 - 5 mm）并将其悬挂在含有Krebs Ringer溶液（37℃，95% O2，5% CO2）的器官浴槽中，以评估内皮和平滑肌反应性。与单独使用CyA的动物相比，用CyA和PTX（40 mg/kg/天）治疗的动物对乙酰胆碱的内皮依赖性舒张作用显著增强（p < 0.05）。对组胺和二磷酸腺苷的反应不受影响。然而，使用PTX（80 mg/kg/天）显著恶化了对相同药物的内皮反应（p < 0.05），表明该浓度的PTX具有有害作用。对硝普钠的非内皮依赖性舒张在所有组中相当。结果表明，PTX对长期暴露于CyA的患者的临床益处可能部分归因于血管内皮功能的改善。然而，高剂量时遇到的毒性应提醒其在临床应用中的使用。
