Mitsuoka W, Egashira S, Tagawa H, Kuga T, Hayashi Y, Yamada A, Tomoike H, Nakamura M, Takeshita A
Research Institute of Angiocardiology and Cardiovascular Clinic, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Cardiovasc Res. 1995 Aug;30(2):246-54.
X-irradiation is known to enhance atherosclerotic change. We tested whether coronary vasoconstrictor responses are augmented at the sites of X-ray-induced intimal thickening in Göttingen miniature pigs.
In 17 pigs, a major branch of the left coronary artery was denuded with a balloon catheter. In 10 pigs, the denuded portion of the left coronary artery was selectively irradiated with 15 Gy of X-rays twice at 3 and 4 months after denudation (group 1). The remaining 7 pigs were not irradiated (group 2). The effects of intracoronary administration of serotonin, histamine and phenylephrine on the coronary diameter were studied 3 (3M) and 5 months (5M) after denudation. After the angiographical study at 5M, the vessels were isolated and isometric tension was measured in an organ chamber.
The percent reduction in coronary diameter evoked with 10 micrograms.kg-1 of serotonin increased from 39(s.e.m. 4)% before X-irradiation (3M) to 75(6)% after X-irradiation (5M) in group 1 (P < 0.01), while it did not differ in group 2 [39(6)% at 3M vs. 33(8)% at 5M[ [39(6)% at 3M vs. 33(8)% at 5M]. In group 1, serotonin-induced coronary constriction was frequently accompanied by ischemic ECG changes. Histamine (10 micrograms.kg-1)-induced vasoconstriction was also augmented but to a smaller degree [47(6)% at 3M vs. 62(4)% at 5M; P < 0.05] in group 1, while it remained unchanged in group 2[52(5)% at 3M vs. 44(7)% at 5M]. Phenylephrine did not cause detectable contraction in either group at 3M or 5M. Methysergide and ketanserin attenuated serotonin-induced hypercontraction in a dose-dependent fashion. In the in vitro studies, endothelium-dependent relaxation to serotonin was impaired at the denuded site with (group 1) and without (group 2) X-irradiation to a similar extent. Isometric tension of medial smooth muscle developed by serotonin was significantly greater at the denuded site with X-irradiation (group 1) than the control site and the denuded site without X-irradiation (group 2) (P < 0.05). Intimal thickening was significantly greater at the denuded sites with X-irradiation [group 1, 238(45) microns] than at the denuded sites without X-irradiation [group 2, 58(5) microns] (P < 0.05).
These results indicate that X-irradiation augments the coronary vasoconstrictor responses to autacoids, predominantly to serotonin, and that this augmentation is accompanied by enhanced intimal thickening. Serotonin-induced hypercontraction after X-irradiation resulted mainly from the hyperreactivity of medial smooth muscle.
已知X射线照射可增强动脉粥样硬化改变。我们测试了在哥廷根小型猪中，X射线诱导的内膜增厚部位的冠状动脉收缩反应是否增强。
对17头猪，用球囊导管剥脱左冠状动脉的一个主要分支。10头猪在剥脱后3个月和4个月时，对左冠状动脉剥脱部分选择性地进行两次15 Gy的X射线照射（第1组）。其余7头猪不进行照射（第2组）。在剥脱后3个月（3M）和5个月（5M）研究冠状动脉内给予血清素、组胺和去氧肾上腺素对冠状动脉直径的影响。在5M进行血管造影研究后，分离血管并在器官浴槽中测量等长张力。
第1组中，10μg.kg-1血清素引起的冠状动脉直径缩小百分比从X射线照射前（3M）的39（标准误4）%增加到照射后（5M）的75（6）%（P<0.01），而第2组无差异[3M时为39（6）%，5M时为33（8）%]。在第1组中，血清素诱导的冠状动脉收缩常伴有缺血性心电图改变。组胺（10μg.kg-1）诱导的血管收缩也增强，但程度较小[3M时为47（6）%，5M时为62（4）%；P<0.05]，而第2组保持不变[3M时为52（5）%，5M时为44（7）%]。在3M或5M时，去氧肾上腺素在两组中均未引起可检测到的收缩。麦角新碱和酮色林以剂量依赖方式减弱血清素诱导的过度收缩。在体外研究中，在有（第1组）和无（第2组）X射线照射的剥脱部位，对血清素的内皮依赖性舒张均受到类似程度的损害。X射线照射的剥脱部位（第1组）由血清素产生的中膜平滑肌等长张力明显大于对照部位和无X射线照射的剥脱部位（第2组）（P<0.05）。X射线照射的剥脱部位的内膜增厚[第1组，238（45）μm]明显大于无X射线照射的剥脱部位[第2组，58（5）μm]（P<0.05）。
这些结果表明，X射线照射增强了冠状动脉对自体活性物质的收缩反应，主要是对血清素的反应，并且这种增强伴随着内膜增厚的增加。X射线照射后血清素诱导的过度收缩主要源于中膜平滑肌的高反应性。
Zotero 插件