Ampa-receptor blockade within the rvlm modulates cardiovascular responses via glutamate during peripheral stimuli

Abstract

We investigated the effects of AMPA-receptor blockade in the rostral ventrolateral medulla (RVLM) on cardiovascular responses and extracellular concentrations of glutamate during two different types of stimuli that activate peripheral A δ - and C-fiber polymodal nociceptors using anesthetized rats. First, mechanical stimulation was achieved by applying a bilateral hindpaw pinch for 5 s, and second, thermal stimulation was evoked by immersing bilaterally the hindpaw metatarsi in a 52∘C hot water bath for 4 s. Mechanical stimulation increased mean arterial pressure (MAP) by 23 ± 1 mmHg and heart rate (HR) by 25 ± 3 bpm (n= 8). Thermal stimuli increased MAP by 32 ± 3 mmHg and HR by 27 ± 4 bpm (n= 8). After controlled generation of mechanical or thermal stimulation, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 1.0 μ M) was microdialysed bilaterally into the RVLM for 30 min. Administration of CNQX attenuated MAP and HR responses during a subsequent mechanical but not during thermal stimulation. Analyses of extracellular concentrations of glutamate within the RVLM bilaterally revealed an increase of this neurotransmitter within the RVLM during mechanical noxious stimulation. Concomitant with attenuation of the cardiovascular responses, glutamate concentrations were also decreased during the mechanical stimulation after administration of CNQX. These results demonstrate that the AMPA-receptor blockade within the RVLM that attenuates cardiovascular responses during mechanical stimulation is associated with a reduction in extracellular levels of glutamate. In addition, it appears that AMPA receptors in the RVLM do not play a role in mediating cardiovascular responses during thermal stimulation.