Bradycardic Responses to Microinjection of L‐Glutamate, AMPA, and NMDA Into the Nucleus Ambiguus (NA) Are Attenuated Following Chronic Intermittent Hypoxia (CIH) in Young Adult F344 Rats

Baroreflex control of heart rate (HR) is reduced following CIH. Since glutamate receptors in vagal cardiac motor neurons in NA are involved in baroreflex bradycardia, we hypothesized that the HR responses to glutamate (Glu) receptor activation is attenuated following CIH. F344 rats (4–5 months) were exposed to either room air (RA; normoxia) or CIH for 35days, and were then anesthetized with sodium pentobarbital. Using a multichannel injector, L‐glu (10 mM, 20 nl; saturation dose), AMPA (0.2 mM/L, 20 nl; saturation dose), and NMDA (4 mM/L, 20 nl; saturation dose) were microinjected into the same location of the left NA (−100 to + 100 μm relative to the caudal end of the area postrema), respectively. We found that CIH reduced the maximal HR response to L‐glu injection (RA: −282 ± 13 vs. CIH: −232 ± 16 bpm; p<0.05) Similarly, CIH reduced the maximal HR response to AMPA injection (RA: −290 ± 30 vs. CIH: −227 ± 15 bpm, p<0.05). CIH also attenuated the maximal HR response to NMDA injection (RA: −302 ± 16, vs. CIH: −238 ± 27 bpm, p<0.05). Thus, our data suggest that selective activation of NMDA and AMPA receptors induce prominent and rapidly evolving bradycardia. The magnitude of bradycardic responses to activation of NMDA and AMPA receptors is similar to the bradycardic responses elicited by L‐glu injection, indicating that roles of these two glutamatergic receptors may not be simply additive. CIH impairs both NMDA and AMPA transmission in NA. This may contribute to attenuation of the baroreflex sensitivity following CIH. NIH AG‐021020.