可乐定、多巴胺、多巴酚丁胺和多培沙明对大鼠胃基础及酸刺激黏膜血流的不同作用。

Differential effects of clonidine, dopamine, dobutamine, and dopexamine on basal and acid-stimulated mucosal blood flow in the rat stomach.

作者信息

Holzer P, Painsipp E

机构信息

Department of Experimental and Clinical Pharmacology, University of Graz, Graz, Austria.

出版信息

Crit Care Med. 2001 Feb;29(2):335-43. doi: 10.1097/00003246-200102000-00021.

DOI:10.1097/00003246-200102000-00021

PMID:11246314

Abstract

OBJECTIVE

To analyze the effects of clonidine, dopamine, dobutamine, and dopexamine on gastric mucosal blood flow (GMBF) at baseline and after stimulation by acid back diffusion through a disrupted gastric mucosal barrier.

DESIGN

Prospective, randomized, unblinded study.

SETTING

University research laboratory.

SUBJECTS

Adult Sprague-Dawley rats.

INTERVENTIONS

Mean arterial blood pressure (MAP) and heart rate (HR) were recorded from a carotid artery of the phenobarbital-anesthetized animals. A jugular vein was cannulated for continuous infusion of saline and intravenous drug administration. The stomach was prepared for luminal perfusion and for recording GMBF with the hydrogen gas clearance technique. Gastric mucosal vascular conductance (GMVC) was calculated as GMBF divided by MAP.

MEASUREMENTS AND MAIN RESULTS

Clonidine (37.5 and 112.5 nmol x kg(-1)) lowered MAP and HR and caused gastric vasodilation as shown by a rise of GMVC. The 2.5-fold increase in GMVC elicited by gastric perfusion with HCl (0.15 M) plus ethanol (25%) was depressed by clonidine. All cardiovascular effects of clonidine were prevented by the alpha2-adrenoceptor antagonist idazoxan (2 micromol x kg(-1)). Infusion of dopamine (15 and 45 micromol x kg(-1) x hr(-1)), dobutamine, or dopexamine (each at 5 and 15 micromol x kg(-1) x hr(-1)) caused tachycardia. GMVC at baseline was attenuated by the higher dose of dopamine and dopexamine, but not dobutamine. In contrast, the acid-induced vasodilation in the gastric mucosa was depressed by dobutamine and dopexamine, but not dopamine.

CONCLUSIONS

Clonidine, dobutamine, and dopexamine at high dosage suppress the gastric mucosal vasodilator response to acid back diffusion, which is an important defense mechanism. Although the dose equivalence between rats and humans is not known, the antivasodilator effects highlight an adverse action whereby large doses of dobutamine, dopexamine, and clonidine may compromise gastric mucosal homeostasis and facilitate stress ulcer formation. Dopamine lacks this detrimental activity.

摘要

目的

分析可乐定、多巴胺、多巴酚丁胺和多培沙明在基础状态下以及通过受损胃黏膜屏障的酸反向弥散刺激后对胃黏膜血流（GMBF）的影响。

设计

前瞻性、随机、非盲研究。

地点

大学研究实验室。

对象

成年斯普拉格-道利大鼠。

干预措施

从苯巴比妥麻醉动物的颈动脉记录平均动脉压（MAP）和心率（HR）。通过颈静脉插管持续输注生理盐水并进行静脉给药。准备胃用于腔内灌注，并采用氢气清除技术记录GMBF。胃黏膜血管传导率（GMVC）计算为GMBF除以MAP。

测量指标及主要结果

可乐定（37.5和112.5 nmol·kg⁻¹）降低MAP和HR，并导致胃血管舒张，表现为GMVC升高。用0.15 M HCl加25%乙醇进行胃灌注引起的GMVC 2.5倍增加被可乐定抑制。可乐定的所有心血管效应均被α₂肾上腺素能受体拮抗剂咪唑克生（2 μmol·kg⁻¹）阻断。输注多巴胺（15和45 μmol·kg⁻¹·hr⁻¹）、多巴酚丁胺或多培沙明（均为5和15 μmol·kg⁻¹·hr⁻¹）引起心动过速。基础状态下的GMVC被较高剂量的多巴胺和多培沙明减弱，但不受多巴酚丁胺影响。相反，多巴酚丁胺和多培沙明抑制胃黏膜酸诱导的血管舒张，但多巴胺无此作用。