Orlandi C, Blackshear J L, Hollenberg N K
Microvasc Res. 1986 Jul;32(1):121-30. doi: 10.1016/0026-2862(86)90048-8.
Evidence that platelet activation contributes to ischemia associated with atherosclerosis led us to examine the response of the limb collateral arterial tree to a platelet product, serotonin. In 23 anesthetized dogs we measured arterial diameter (angiography) and blood flow (133Xe transit) before or 2 weeks after superficial femoral artery ligation (SFAL). In normal hindlimbs blood flow increased after 5-hydroxytryptamine (5-HT) and there was a modest but measurable, dose dependent narrowing of 1- to 2-mm vessels, the major stem vessels for collateral blood flow. After SFAL, identical segments of these vessels responded to serotonin more: the slope relating dose and response became steeper (P less than 0.001), the threshold dose fell significantly (P less than 0.001), and calf blood flow fell. The vasodilator response to acetylcholine was reduced sharply after SFAL, but was still demonstrable. The 5-HT-2 serotonin antagonist, ketanserin, reversed serotonin induced spasm in the region served by collaterals (P less than 0.025). Responses to norepinephrine were not potentiated. A 5-HT-2 receptor dependent sensitization of collateral arterial vessels, and blunting of the normal vasodilator response, mediates a paradoxical decrease in perfusion induced by 5-HT in regions served by the collaterals.
血小板激活会导致与动脉粥样硬化相关的局部缺血,这一证据促使我们研究肢体侧支动脉树对一种血小板产物——血清素的反应。在23只麻醉犬中,我们在股浅动脉结扎(SFAL)前或2周后测量了动脉直径(血管造影)和血流量(133Xe通过时间)。在正常后肢,5-羟色胺(5-HT)作用后血流量增加,1至2毫米的血管(侧支血流的主要主干血管)出现适度但可测量的剂量依赖性狭窄。SFAL后,这些血管相同节段对血清素的反应更强:剂量与反应关系的斜率变得更陡(P<0.001),阈剂量显著降低(P<0.001),小腿血流量下降。SFAL后对乙酰胆碱的血管舒张反应急剧降低,但仍可检测到。5-HT-2血清素拮抗剂酮色林可逆转侧支供血区域血清素诱导的痉挛(P<0.025)。对去甲肾上腺素的反应未增强。侧支动脉血管的5-HT-2受体依赖性致敏以及正常血管舒张反应的减弱,介导了5-HT在侧支供血区域引起的灌注反常性降低。