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可乐定在离体灌注兔肾中通过突触前α-肾上腺素能受体介导的前列腺素释放效应

Prejunctional alpha-adrenoceptor mediated prostaglandin releasing effect of clonidine in the isolated perfused rabbit kidney.

作者信息

Ercan Z S

出版信息

Arch Int Pharmacodyn Ther. 1983 Sep;265(1):138-49.

PMID:6316860
Abstract

The effects of clonidine (CLO) were assessed in the isolated perfused rabbit kidney on responses to periarterial stimulation (PS) and intraarterially injected noradrenaline (NA). Changes in perfusion pressure (PP) and responses of venous outflow-superfused assay organs to PS and NA were considered as parameters. Graded increases in PP and contractions of venous outflow-superfused rabbit aortic strips were elicited by PS at frequencies of 5-10 Hz and intraarterially injected NA at concentrations of 10(-8) - 10(-7) M. CLO added to the perfusion medium caused concentration-dependent reductions of PP and of aorta contractions to PS. The inhibitory effect of CLO was reversed by acetylsalicylic acid (ASA). The responses to venous outflow-superfused rat stomach fundus strip to PS and exogenous NA were biphasic. The first relaxation phase to PS was reduced but the second contractile phase was enhanced by CLO. Responses to exogenous NA in PP and venous outflow-superfused organs were not affected by CLO. The relaxation of submaximally contracted and kidney venous effluent-superfused cat tracheal muscle to PS was reduced whereas the responses to NA was unaffected by CLO. The inhibitory effect of CLO on PS in the cat tracheal muscle was prevented by yohimbine (YOH). YOH, however, caused a further decrease in PP in response to both PS and exogenous NA. From these results it was concluded that CLO may act on presynaptic alpha-adrenoceptors in the kidney resulting in a reduction on the release of NA and enhancement of the synthesis of prostaglandins (PGs).

摘要

在离体灌注兔肾中评估可乐定(CLO)对动脉周围刺激(PS)和动脉内注射去甲肾上腺素(NA)反应的影响。灌注压力(PP)的变化以及静脉流出超灌注试验器官对PS和NA的反应被视为参数。在5 - 10Hz频率下的PS以及动脉内注射浓度为10⁻⁸ - 10⁻⁷M的NA可引起PP的分级增加以及静脉流出超灌注兔主动脉条的收缩。添加到灌注介质中的CLO导致PP以及主动脉对PS收缩的浓度依赖性降低。乙酰水杨酸(ASA)可逆转CLO的抑制作用。静脉流出超灌注大鼠胃底条对PS和外源性NA的反应是双相的。CLO使对PS的第一个舒张期降低,但使第二个收缩期增强。CLO不影响PP以及静脉流出超灌注器官对外源性NA的反应。亚最大收缩且肾静脉流出超灌注猫气管肌对PS的舒张作用降低,而对NA的反应不受CLO影响。育亨宾(YOH)可阻止CLO对猫气管肌中PS的抑制作用。然而,YOH会导致对PS和外源性NA反应时PP进一步降低。从这些结果得出结论,CLO可能作用于肾中的突触前α-肾上腺素能受体,导致NA释放减少以及前列腺素(PGs)合成增强。

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