Serotonin induced vasodilatation in the human forearm is antagonized by the selective 5-HT3 receptor antagonist ICS 205-930.
Serotonin induced vasodilatation in the human forearm is antagonized by the selective 5-HT3 receptor antagonist ICS 205-930.
复制标题
选择性 5-HT3 受体拮抗剂 ICS 205-930 可拮抗人前臂中血清素诱导的血管舒张。
DOI：
10.1016/0024-3205(88)90255-x
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
P. V. van Zwieten
中科院分区：
文献类型：
--
作者：
G. Blauw;P. van Brummelen;P. V. van Zwieten
在7名健康青年志愿者(22-32岁)的前臂，观察了5-HT3受体在5-羟色胺(5-羟色胺；5-羟色胺)双相血管扩张反应中的作用。单次注入5-羟色胺(1 ng/kg/min)和乙酰胆碱(ACh，500 ng/kg/min)。5-羟色胺和选择性5-HT3受体拮抗剂ICS 205-930(350和700 ng/kg/min)和ACh与ICS 205-930(700 ng/kg/min)联合输注。停药至少1小时后，重复单次输注5-羟色胺和乙酰胆碱。随后，5-羟色胺和乙酰胆碱与阿托品(100 ng/kg/min)同时静脉滴注。用R波触发静脉闭塞体积描记仪测定前臂血流量。心率(HR)和I.A.半连续记录血压。所用剂量的药物均未引起全身血流动力学效应。在空腹血流量快速增加316±55%后，5-羟色胺引起的空腹血流量持续增加90±22%(均值±扫描电子显微镜，p<；两者均为0.05)。ACh引起的单相血管扩张为475±123%(p<；0.05)。ICS205-930350 ng/kg/min(p=0.057，n=5)和700 ng/kg/min(p<；0.05，n=7)均可减弱5-羟色胺的短暂和持续性扩张反应。ICS205-930的最大剂量对ACh的扩张器反应无显著影响。阿托品可阻断ACh引起的血管扩张(p<；0.05)，但不影响5-羟色胺的双相扩张反应。ICS 205-930可拮抗5-羟色胺引起的双相血管扩张，提示该反应是通过激活5-HT3受体实现的。阿托品不影响血管对5-羟色胺的反应，提示5-羟色胺不是通过胆碱能神经末梢释放ACh间接引起血管松弛的。
The role of 5-HT3receptors in the biphasic vasodilatator response to serotonin (5-hydroxytryptamine; 5-HT) was investigated in the forearm of 7 young healthy volunteers (aged 22–32 years). Single dose infusions of 5-HT (1 ng/kg/min) and of acetylcholine (ACh, 500 ng/kg/min) were administered into the brachial artery. Subsequently combined infusions of 5-HT together with the selective 5-HT3receptor antagonist ICS 205–930 (350 and 700 ng/kg/min), and ACh together with ICS 205–930 (700 ng/kg/min) were given. After a pause of at least 1 hour the single infusions of 5-HT and ACh were repeated. Subsequently, 5-HT and ACh were infused together with atropine (100 ng/kg/min). Forearm blood flow (FBF) was measured by R-wave triggered venous occlusion plethysmography. Heart rate (HR) and i.a. blood pressure (BP) were recorded semi-continuously. None of the drugs in the doses used did induce systematic hemodynamic effects. After an initial rapid transient increase in FBF of 316 ± 55%, 5-HT elicited a persistent increase in FBF of 90 ± 22% (mean ± SEM, p<0.05 for both). ACh induced a monophasic vasodilatation of 475 ± 123% (p<0.05). Both the initial transient and the persistent dilatator response to 5-HT were attenuated by ICS 205–930 350 ng/kg/min (p=0.057, n=5) and 700 ng/kg/min (p<0.05, n=7). The highest dose of ICS 205–930 did not significantly influence the dilatator response to ACh. Atropine abolished the ACh induced vasodilatation (p<0.05), but did not influence the biphasic dilatator response to 5-HT. Thus the 5-HT induced biphasic vasodilatation was antagonized by ICS 205–930, indicating that this response was mediated by 5-HT3receptor activation. The fact that atropine did not influence the vascular response to 5-HT suggests that 5-HT did not induce vascular relaxation indirectly by the release of ACh from cholinergic nerve endings.