HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 92/5/849    most recent expphysiol.2007.037861v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wang, L.-G. Articles by Wang, W.-Z. Search for Related Content PubMed PubMed Citation Articles by Wang, L.-G. Articles by Wang, W.-Z.

Departments of ¹ Physiology³ Pharmacology, Second Military Medical University, Shanghai 200433, China ² Department of Neurosurgery, Zhongshan Hospital, University of Xiamen, Xiamen 361004, China

The depressor mechanism of imidazoline-like drugs is believed to result from activation of I₁-imidazoline receptors (I₁R) and/or ₂-adrenoceptors within the central nervous system, which are associated with the glutamatergic system. The rostral ventrolateral medulla (RVLM) has been recognized as a specific target area that mediates the depressor action of imidazoline-like drugs. The objective of this study was to determine the comparative effects of blockade of the central glutamate receptor subtypes N-methyl-D-aspartate (NMDA) or -amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate on the cardiovascular actions of imidazoline-like drugs (clonidine and moxonidine) in anaesthetized rats. Intracerebroventricular (I.C.V.) injection of the NMDA receptor antagonist MK801 or the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) produced similar reductions in blood pressure (BP) and heart rate (HR) to those induced by I.C.V. injection of clonidine. Intracerebroventricular injection of the glutamate receptor antagonist kynurenic acid not only abolished clonidine-induced hypotension and bradycardia but converted the responses to a pressor action and tachycardia. Unilateral injection of MK801 or CNQX into RVLM significantly attenuated intra-RVLM clonidine-induced decreases in BP and HR. We also found that unilateral injection of a selective I₁R agonist, moxonidine, significantly decreased BP and HR, which were also attenuated to a similar extent by prior injection of MK801 or CNQX. In conclusion, these data show that blockade of central (RVLM) NMDA and AMPA/kainate receptors produces similar attenuation of the decrease in BP and HR induced by clonidine or moxonidine. It is suggested that both NMDA and AMPA/kainate receptors are involved in the cardiovascular inhibition produced by imidazoline-like drugs, which is probably at least partly dependent on an I₁R mechanism in the RVLM.

(Received 15 March 2007; accepted after revision 11 June 2007; first published online 15 June 2007)
Corresponding author W.-Z. Wang: Department of Physiology, Second Military Medical University, 800 Xiang-Yin Road, Shanghai 200433, China. Email: wangwz68{at}hotmail.com