Ionotropic Glutamate Receptors Partially Mediate Pressor and Sympathoexcitatory Responses to Disinhibition of the RVLM after Sinoaortic Denervation and Contralateral RVLM Inhibition in Sedentary and Physically Active Rats

The RVLM is a bilateral brainstem region important for sympathetic control of arterial pressure (AP). We have demonstrated that after sinoaortic denervation (SAD) and unilateral blockade of RVLM, GABA A receptor blockade (GABA A ‐X) in RVLM dramatically increased splanchnic sympathetic nerve activity (SSNA) and AP in sedentary (SED) and wheel running (WR) rats. Whether this excitation is mediated by glutamate is unknown. We tested the hypotheses that 1) ionotropic glutamate receptors (iGluRs) contribute to increases in AP and SSNA in response to GABA A ‐X and 2) SED conditions enhance glutamatergic excitation. Prior to microinjections in Inactin‐anesthetized SED (n=6) and WR (n=5) rats, SAD was performed and one RVLM was inhibited (muscimol 2mM, 90nl). Responses to GABA A ‐X using bicuculline (Bic 5mM, 90nl) alone and in the presence of the iGluR antagonist kynurenic acid (Kyn 40mM, 90nl) were tested in the contralateral, intact RVLM. As before GABA A ‐X alone increased AP and SSNA in SEDs and WRs. Pretreatment with Kyn attenuated increases in AP in SEDs (Δ49±13 mmHg vs Δ24±4 mmHg) and WRs (Δ30±5 mmHg vs. Δ11±5 mmHg) (p<0.05 main effect). However, effects of pretreatment with kyn on increases in SSNA did not reach significance (SEDs: Δ121±28 % vs Δ81±13 %; WRs: Δ97±46 % vs Δ65±30 %) (p=0.149 main effect). Our preliminary data suggests that blockade of endogenous glutamate limits pressor responses to removal of GABA input in the RVLM of barodenervated rats. The residual sympathoexcitation appears to be due to non‐ionotropic glutamatergic input to RVLM that may or may not be altered in SEDs and WRs. R01‐HL096787; R01‐HL096787‐S1