NMDA receptors in caudal ventrolateral medulla mediate reflex airway dilation arising from the hindlimb

The caudal ventrolateral medulla (CVLM) has been shown to participate in the reflex airway dilation evoked by stimulation of thin fiber afferents innervating the hindlimb of anesthetized dogs. Nevertheless, the pharmacological mechanism in the CVLM by which hindlimb afferents evoke this reflex airway dilation is not known. Therefore, we examined the role played by excitatory amino acid receptors in the CVLM in the reflex airway dilation arising from the hindlimb. Using chloralose-anesthetized dogs, we found that bilateral microinjections into the CVLM of either (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (25 mM, 50 nl) or (+/-)-2-amino-5-phosphonovaleric acid (50 mM, 50 nl), both of which block N-methyl-D-aspartate (NMDA) receptors, reversibly attenuated the decrease in total lung resistance that was evoked by either electrical stimulation of C-fibers in the sciatic nerve or by static contraction of both gastrocnemius muscles. In contrast, bilateral microinjection into the CVLM of 6-cyano-7-nitroquinoxaline-2,3-dione (39 microM, 50 nl), which blocks non-NMDA receptors, augmented the reflex decrease in total lung resistance that was evoked by either sciatic nerve stimulation or contraction of the gastrocnemius muscles. Bilateral microinjections of xanthurenic acid (100 mM, 50 nl) into the CVLM had no effect on the decrease in total lung resistance that was evoked by sciatic nerve stimulation. We conclude that NMDA, but not non-NMDA, receptors in the CVLM play an important role in the reflex arc that dilates the airways when hindlimb afferents are stimulated by either muscular contraction or electrical stimulation.