AMPA-receptor blockade within the RVLM modulates cardiovascular responses via glutamate during peripheral stimuli

We investigated the effects of AMPA-receptor blockade in the rostral ventro lateral medulla (RVLM) on cardiovascular responses and extracellular concen trations of glutamate during two different types of stimuli that activate p eripheral A delta- and C-fiber polymodal nociceptors using anesthetized rat s. First, mechanical stimulation was achieved by applying a bilateral hindp aw pinch for 5 s, and second, thermal stimulation was evoked by immersing b ilaterally the hindpaw metatarsi in a 52 degreesC hot water bath for 3 s. M echanical stimulation increased mean arterial pressure (MAP) by 23 +/- 1 mm Hg and heart rate (HR) by 25 +/- 3 bpm (n = 8). Thermal stimuli increased M AP by 32 +/- 3 mmHg and HR by 27 +/- 3 bpm (n = 8). After controlled genera tion of mechanical or thermal stimulation, 6-cyano-7-nitroquinoxaline-2,3-d ione (CNQX; 1.0 muM) was microdialysed bilaterally into the RVLM for 30 min . Administration of CNQX attenuated MAP and HR responses during a subsequen t mechanical but not during thermal stimulation. Analyses of extracellular concentrations of glutamate within the RVLM bilaterally revealed an increas e of this neurotransmitter within the RVLM during mechanical noxious stimul ation. Concomitant with attenuation of the cardiovascular responses, glutam ate concentrations were also decreased during the mechanical stimulation af ter administration of CNQX. These results demonstrate that the AMPA-recepto r blockade within the RVLM that attenuates cardiovascular responses during mechanical stimulation is associated with a reduction in extracellular leve ls of glutamate. In addition, it appears that AMPA receptors in the RVLM do not play a role in mediating cardiovascular responses during thermal stimu lation. (C) 2001 Academic Press.