Niimi Y, Azuma H, Hirakawa K
Department of Neurosurgery, Tokyo Medical and Dental University, Japan.
Am J Physiol. 1994 Apr;266(4 Pt 2):H1348-56. doi: 10.1152/ajpheart.1994.266.4.H1348.
To evaluate the significance of repeated denudation injury in progression of atherosclerosis, we performed a single and then a second balloon denudation on the rabbit carotid arteries. Morphological examinations and organ chamber experiments were performed, and the results were compared. On morphological examinations, reendothelialization was almost completed in 2 wk after redenudation, whereas it required 6 wk after a single denudation. Intimal thickening progressed after redenudation. Organ chamber experiments showed that contractile responses and endothelium-independent relaxation remained unchanged after redenudation. Endothelium-dependent relaxations to acetylcholine, ADP, and substance P decreased progressively by repeating denudation. These relaxation responses were inhibited by NG-nitro-L-arginine, hemoglobin, and methylene blue and were considered to be associated with the production and/or release of endothelium-derived relaxing factor-nitric oxide (EDRF-NO). The diffusion barrier mechanism for the decreased endothelium-dependent relaxations was ruled out using sandwich experiments. In conclusion, repeated endothelial denudation caused progression of intimal thickening and acceleration of endothelial regeneration, and repeated endothelial regeneration resulted in progressively less production and/or release of EDRF-NO.
为评估反复剥脱损伤在动脉粥样硬化进展中的意义，我们对兔颈动脉进行了一次球囊剥脱，然后又进行了第二次球囊剥脱。进行了形态学检查和器官腔实验，并对结果进行了比较。在形态学检查中，再次剥脱后2周内膜再内皮化几乎完成，而单次剥脱后则需要6周。再次剥脱后内膜增厚进展。器官腔实验表明，再次剥脱后收缩反应和内皮依赖性舒张保持不变。反复剥脱后，对乙酰胆碱、ADP和P物质的内皮依赖性舒张逐渐降低。这些舒张反应被NG-硝基-L-精氨酸、血红蛋白和亚甲蓝抑制，被认为与内皮源性舒张因子一氧化氮（EDRF-NO）的产生和/或释放有关。通过夹心实验排除了内皮依赖性舒张降低的扩散屏障机制。总之，反复内皮剥脱导致内膜增厚进展和内皮再生加速，反复内皮再生导致EDRF-NO的产生和/或释放逐渐减少。
