title: Comparative study of NMDA and AMPA/kainate receptors involved in cardiovascular inhibition produced by imidazoline-like drugs in anaesthetized rats.
abstract: The depressor mechanism of imidazoline-like drugs is believed to result from activation of I(1)-imidazoline receptors (I(1)R) and/or alpha(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 alpha-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 I(1)R 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 I(1)R mechanism in the RVLM.
authors.affiliation: Department of Physiology, Second Military Medical University, 800 Xiang-Yin Road, Shanghai 200433, China.
authors.forename: Li-Gang
authors.initials: LG
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Zeng
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Yuan
authors.forename: Ding-Feng
authors.initials: DF
authors.lastname: Su
authors.forename: Wei-Zhong
authors.initials: WZ
authors.lastname: Wang
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D054755:Imidazoline Receptors; D007276:Injections, Intraventricular; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology; D011955:Receptors, Drug / Q000819:agonists; D017470:Receptors, Glutamate / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology
chemical_list: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000959:Antihypertensive Agents; D003000:Clonidine; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D007093:Imidazoles; D054755:Imidazoline Receptors; D007736:Kynurenic Acid; D018091:Receptors, AMPA; D011955:Receptors, Drug; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; C043482:moxonidine