慢性中枢内皮素-1对清醒大鼠血流动力学和血浆血管加压素的影响。

Effect of chronic central endothelin-1 on hemodynamics and plasma vasopressin in conscious rats.

作者信息

Rossi Noreen F, Zhang Fong, Chen Haiping

机构信息

Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA.

出版信息

Neurol Res. 2011 Mar;33(2):169-75. doi: 10.1179/016164111X12881719352336.

DOI:10.1179/016164111X12881719352336

PMID:21801591

Abstract

OBJECTIVES

These studies were designed to test whether chronic central administration of endothelin-1 induces changes in systemic hemodynamics and plasma vasopressin similar to those observed with acute microinjections of endothelin-1.

METHODS

Sprague Dawley rats underwent sham denervation or sinoaortic denervation. Three days later, baseline mean arterial blood pressure, heart rate, and vasopressin were assessed in conscious rats. Then, a cannula was stereotaxically inserted into the lateral ventricle and attached to an osmotic minipump that delivered one of the following: (i) artificial cerebrospinal fluid; (ii) endothelin-1, 10 pmol/hour; (iii) BQ-123, 400 pmol/hour; or (iv) endothelin-1+BQ-123. Mean arterial blood pressure and heart rate were monitored daily and blood was obtained for plasma vasopressin on days 3 and 9. On day 10, the rats were euthanized, the hypothalami were removed, and vasopressin messenger ribonucleic acid content was assessed.

RESULTS

The pressor effect of intracerebroventricular endothelin-1 was similar in intact and sinoaortic denervation rats and was prevented by endothelin receptor A antagonism with BQ-123. Administration of BQ-123 alone resulted in a depressor and bradycardia in sinoaortically denervated rats. Chronic endothelin-1 administration did not change plasma vasopressin but resulted in a significant decrease in hypothalamic vasopressin messenger ribonucleic acid levels, which was reversed by endothelin receptor A inhibition.

DISCUSSION

Although the pressor effect of chronic central endothelin-1 is similar to that reported with acute endothelin-1, plasma vasopressin levels do not increase, at least in part, due to downregulation of hypothalamic vasopressin gene expression. Sinoaortic denervation increases endogenous central endothelin receptor A tone. Furthermore, these observations confirm that the pressor effect of central endothelin-1 is not mediated by plasma vasopressin.

摘要

目的

这些研究旨在测试长期经中枢给予内皮素 -1 是否会引起全身血流动力学和血浆血管加压素的变化，这些变化类似于急性微量注射内皮素 -1 时所观察到的变化。

方法

将斯普拉格 - 道利大鼠进行假去神经支配或窦主动脉去神经支配。三天后，在清醒大鼠中评估基线平均动脉血压、心率和血管加压素。然后，通过立体定位将套管插入侧脑室，并连接到一个渗透微型泵，该泵输送以下物质之一：（i）人工脑脊液；（ii）内皮素 -1，10 pmol/小时；（iii）BQ -123，400 pmol/小时；或（iv）内皮素 -1 + BQ -123。每天监测平均动脉血压和心率，并在第3天和第9天采集血液以测定血浆血管加压素。在第10天，对大鼠实施安乐死，取出下丘脑，并评估血管加压素信使核糖核酸含量。

结果

完整大鼠和窦主动脉去神经支配大鼠中，脑室内注射内皮素 -1 的升压作用相似，并且用 BQ -123 拮抗内皮素 A 受体可阻止这种作用。单独给予 BQ -123 会导致窦主动脉去神经支配大鼠出现降压和心动过缓。长期给予内皮素 -1 不会改变血浆血管加压素，但会导致下丘脑血管加压素信使核糖核酸水平显著降低，而内皮素 A 受体抑制可使其逆转。