Comparative study of NMDA and AMPA/kainate receptors involved in cardiovascular inhibition produced by imidazoline‐like drugs in anaesthetized rats

The depressor mechanism of imidazoline‐like drugs is believed to result from activation of I 1 ‐imidazoline receptors (I 1 R) and/or α 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 α‐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.