PDF(Pubmed)
Abstract：
To better understand mechanisms of serotonin- (5-HT) mediated vasorelaxation, isolated lateral saphenous veins from cattle were assessed for vasoactivity using myography in response to increasing concentrations of 5-HT or selective 5-HT receptor agonists. Vessels were pre-contracted with 1 × 10-4 M phenylephrine and exposed to increasing concentrations of 5-HT or 5-HT receptor agonists that were selective for 5-HT1B, 5-HT2B, 5-HT4, and 5-HT7. Vasoactive response data were normalized as a percentage of the maximum contractile response induced by the phenylephrine pre-contraction. At 1 × 10-7 M 5-HT, a relaxation was observed with an 88.7% decrease (p < 0.01) from the phenylephrine maximum. At 1 × 10-4 M 5-HT, a contraction was observed with a 165% increase (p < 0.01) from the phenylephrine maximum. Increasing concentrations of agonists selective for 5-HT2B, 5-HT4, or 5-HT7 resulted in a 27%, 92%, or 44% (p < 0.01) decrease from the phenylephrine maximum, respectively. Of these 5-HT receptor agonists, the selective 5-HT4 receptor agonist resulted in the greatest potency (-log EC50) value (6.30) compared with 5-HT2B and 5-HT7 receptor agonists (4.21 and 4.66, respectively). To confirm the involvement of 5-HT4 in 5-HT-mediated vasorelaxation, blood vessels were exposed to either DMSO (solvent control) or a selective 5-HT4 antagonist (1 × 10-5 M) for 5-min prior to the phenylephrine pre-contraction and 5-HT additions. Antagonism of the 5-HT4 receptor attenuated the vasorelaxation caused by 5-HT. Approximately 94% of the vasorelaxation occurring in response to 5-HT could be accounted for through 5-HT4, providing strong evidence that 5-HT-mediated vasorelaxation occurs through 5-HT4 activation in bovine peripheral vasculature.
摘要：
为了更好地理解5-羟色胺（5-HT）介导的血管舒张机制，对5-HT或选择性5-HT受体激动剂浓度增加的反应，使用肌电图检查评估了牛中分离的侧隐静脉的血管活性。用1×10-4M去氧肾上腺素预收缩血管，并暴露于对5-HT1B具有选择性的递增浓度的5-HT或5-HT受体激动剂，5-HT2B,5-HT4和5-HT7。将血管活性反应数据标准化为由去氧肾上腺素预收缩诱导的最大收缩反应的百分比。在1×10-7M5-HT，观察到松弛,从去氧肾上腺素最大值下降88.7%(p<0.01)。在1×10-4M5-HT，从去氧肾上腺素最大值观察到收缩增加165%(p<0.01)。增加对5-HT2B有选择性的激动剂的浓度，5-HT4或5-HT7导致27％，92%,或从去氧肾上腺素最大值降低44%(p<0.01)，分别。在这些5-HT受体激动剂中，与5-HT2B和5-HT7受体激动剂(分别为4.21和4.66)相比,选择性5-HT4受体激动剂产生了最大的效价(-logEC50)值(6.30).为了证实5-HT4参与5-HT介导的血管舒张，在去氧肾上腺素预收缩和添加5-HT之前，将血管暴露于DMSO（溶剂对照）或选择性5-HT4拮抗剂（1×10-5M）5分钟。5-HT4受体的拮抗作用减弱了5-HT引起的血管舒张。响应于5-HT发生的大约94%的血管舒张可以通过5-HT4来解释,这提供了有力的证据表明5-HT介导的血管舒张通过牛外周血管系统中的5-HT4活化而发生。
