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清醒状态下经窦-主动脉去神经大鼠中8-羟基-2-(二正丙基氨基)四氢萘(8-OH-DPAT)与可乐定心血管效应的比较。

Comparison between the cardiovascular effects of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and clonidine in the conscious sino-aortic denervated rat.

作者信息

Petty M A, Kintz J, Di Francesco G F, Fozard J R

机构信息

Merrell Dow Research Institute, Strasbourg Research Center, France.

出版信息

J Auton Pharmacol. 1988 Dec;8(4):267-76. doi: 10.1111/j.1474-8673.1988.tb00569.x.

Abstract
  1. The purpose of this study was to investigate the role of an intact baroreceptor reflex mechanism in the expression of the cardiovascular response to 8-OH-DPAT and to determine whether there are any differences between the activation of central alpha 2-adrenoreceptors and 5-HT1A receptors in this respect. To this end, the effects of 8-OH-DPAT and clonidine have been assessed on blood pressure, heart rate, ECG and cardiac contractility indices in conscious sino-aortic baroreceptor denervated (SAD) rats and their sham-operated controls. 2. In both sham-operated and SAD rats, intravenous (i.v.) administration of 8-OH-DPAT (32 micrograms kg-1) and clonidine (8 micrograms kg-1) produced falls in systemic blood pressure, left ventricular systolic pressure and dP/dtmax. 3. 8-OH-DPAT produced similar bradycardia in each group of rats; in contrast, clonidine had a greater effect in the SAD animals. Increases of the PQ interval mirrored the heart-rate changes with both compounds. 4. No significant changes in end diastolic blood pressure or in the myocardial contractility indices dP/dtmax/P and Vmax were evident. 5. This study provides support for the view that i.v. 8-OH-DPAT lowers blood pressure and heart rate through a central mechanism. The effects occur independently of an intact baroreceptor reflex and are not associated with effects on myocardial contractility. 8-OH-DPAT shows close qualitative similarities to clonidine in this model.
摘要
  1. 本研究的目的是探讨完整的压力感受器反射机制在对8-羟基二苯丙氨酸(8-OH-DPAT)心血管反应表达中的作用,并确定在这方面中枢α2-肾上腺素能受体和5-羟色胺1A(5-HT1A)受体的激活是否存在差异。为此,已评估了8-OH-DPAT和可乐定对清醒的去窦主动脉压力感受器(SAD)大鼠及其假手术对照的血压、心率、心电图和心脏收缩性指标的影响。2. 在假手术和SAD大鼠中,静脉注射(i.v.)8-OH-DPAT(32微克/千克)和可乐定(8微克/千克)均导致全身血压、左心室收缩压和dP/dtmax下降。3. 8-OH-DPAT在每组大鼠中产生相似的心动过缓;相比之下,可乐定对SAD动物的作用更大。两种化合物导致的PQ间期延长反映了心率变化。4. 舒张末期血压或心肌收缩性指标dP/dtmax/P和Vmax无明显变化。5. 本研究支持以下观点:静脉注射8-OH-DPAT通过中枢机制降低血压和心率。这些作用独立于完整的压力感受器反射而发生,且与对心肌收缩性的影响无关。在该模型中,8-OH-DPAT与可乐定在性质上表现出密切的相似性。

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