Submitted on April 5, 2007
Accepted on June 15, 2007
Contribution of AMPA/ kainate receptors in the rostral ventrolateral medulla to the hypotensive and sympathoinhibitory effects of clonidine
Wei-Zhong Wang1*, Li-Gang Wang2, Lie Gao3, and Wei Wang4
1 Department of Physiology, Second Military Medical University, Shanghai, China
2 Department of Physiology, Second Military Medical University, Shanghai, China; Shanghai, China
3 Department of Cellular and Integrative Physiology, University of Nebraska College of Medicine, Omaha, Nebraska, United States
4 Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, Nebraska, United States
* To whom correspondence should be addressed. E-mail: wangwz68{at}hotmail.com.
The depressor and sympathoinhibitory effect of the imidazoline drug clonidine is reported to be associated with functional states of the central glutamate receptors. The rostral ventrolateral medulla (RVLM) has been recognized as a specific target area for mediating the central depressor mechanism of clonidine. The objective of this study was to determine the role of the glutamate receptor subtype alpha-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor within the RVLM in clonidine-induced depressor and sympathoinhibitory action in anesthetized normotensive rats. Unilateral microinjection of 200 pmol of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a potent AMPA/kainate receptor antagonist, into the RVLM completely abolished the pressor action evoked by AMPA (5 pmol) without affecting that the pressor action of N-methyl-D-aspartate (20 pmol). Pretreatment with intra-RVLM injection of CNQX (20 and 200 pmol) dose-dependently attenuated the reduction in blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA) elicited by intra-RVLM clonidine (5 nmol) or intravenous clonidine (10 µg/kg), while 2 pmol of CNQX did not alter clonidine-induced cardiovascular action. Furthermore, the decreases in BP, HR, and RSNA evoked by intravenous clonidine (10 µg/kg) or intra-RVLM clonidine (5 nmol) were reserved when CNQX (20 and 200 pmol) was subsequently injected into the RVLM. In conclusion, these data show that blockade of AMPA/kainate receptors in the RVLM significantly antagonizes decreases in BP, HR, and sympathetic activity induced by clonidine, suggesting that the AMPA/kainate receptors within the RVLM contribute to the depressor and sympathoinhibitory effect of clonidine.
