Changes in systemic and regional haemodynamics during 5-HT7 receptor-mediated depressor responses in rats
Changes in systemic and regional haemodynamics during 5-HT7 receptor-mediated depressor responses in rats
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DOI：
10.1007/pl00005359
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发表时间：
1999-04-01
影响因子：
3.6
通讯作者：
Saxena, PR
中科院分区：
文献类型：
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作者：
De Vries, P;De Visser, PA;Saxena, PR
5-羟色胺（5-HT）诱导的大鼠迟发性降压反应主要由血管5-HT_7受体介导。本研究致力于确定在这种反应过程中的全身和区域血液动力学变化，特别强调局部血管床，可能有助于增加全身血管传导。在用5-HT 2受体拮抗剂利坦色林（50 μ g kg（-1），i. v.）预处理的迷走交感神经切除的戊巴比妥麻醉大鼠中，5-HT（1、3和10 μ g kg（-1）min（-1）10 min; i.v.）产生剂量依赖性的平均动脉血压下降高达46+/-3%。这种降低伴随全身血管传导性增加高达83+/-15%;心输出量不受影响。5-HT使骨骼肌、尸体、肠系膜/胰腺和肾上腺的局部血管传导性分别增加740+/-141%，117+/-18%，135+/-26%和88+/-22%，但使“肺”（主要是动静脉吻合）传导性降低81+/-2%。用R（+）麦角脲（100 μ g kg（-1），i. v.）消除了所有5-HT诱导的全身和局部血液动力学效应。相反，静脉注射S（-）麦角脲（100 μ g kg（-1））或GR 127935（300 μ g kg（-1））预处理不影响5-HT诱导的全身血液动力学变化。上述结果表明，通过5-HT 7受体激活诱导的低血压完全是由全身血管系统的血管舒张引起的，局限于骨骼肌、尸体、肠系膜/胰腺和肾上腺血管床。此外，这项研究表明，血管舒张剂5-HT 7受体的阻滞剂麦角乙脲是立体选择性的。
The 5-hydroxytryptamine (5-HT)-induced late depressor response in rats is mainly mediated by vascular 5-HT7 receptors. The present study was devoted to determining the systemic and regional haemodynamic changes during this response, with particular emphasis on localising vascular beds that may contribute to the increase in total systemic vascular conductance. In vagosympathectomised, pentobarbital-anaesthetised rats pretreated with the 5-HT2 receptor antagonist ritanserin (50 mu g kg(-1), i.v.), 5-HT (1, 3 and 10 mu g kg(-1) min(-1) during 10 min; i.v.) produced a dose-dependent decrease in mean arterial blood pressure by up to 46+/-3%. This decrease was accompanied by increases in systemic vascular conductance by up to 83+/-15%; cardiac output was unaffected. 5-HT increased regional vascular conductance in skeletal muscle, carcass, mesentery/pancreas and adrenals by up to 740+/-141%, 117+/-18%, 135+/-26% and 88+/-22%, respectively, but decreased 'lung' (mainly arteriovenous anastomotic) conductance by up to 81+/-2%. Pretreatment with R(+)lisuride (100 mu g kg(-1), i.v.) abolished all 5-HT-induced systemic and regional haemodynamic effects. In contrast, i.v. pretreatment with S(-)lisuride (100 mu g kg(-1)) or GR127935 (300 mu g kg(-1)) did not affect the 5-HT-induced systemic haemodynamic changes. The above results suggest that hypotension induced via 5-HT7 receptor activation was exclusively caused by vasodilatation of the systemic vasculature, confined to skeletal muscle, carcass, mesentery/pancreaa and adrenal vascular beds. Furthermore, this study shows that blockade of vasorelaxant 5-HT7 receptors by lisuride is stereoselective.