Tonic Glutamatergic Input in the Rostral Ventrolateral Medulla Is Increased in Rats With Chronic Heart Failure

Tonic Glutamatergic Input in the Rostral Ventrolateral Medulla Is Increased in Rats With Chronic Heart Failure by Wei-Zhong Wang, Lie Gao, Han-Jun Wang, Irving H. Zucker, Wei Wang This is a paper from the Nebraska group in which they looked at tonic excitation of the RVLM in chronic heart failure (CHF) rats. Microinjections of kynurenic acid (NMDA and AMPA receptor antagonist), AP5 (NMDA receptor antagonist), or CNQX (AMPA receptor antagonist) into the RVLM of CHF but not sham rats each reduced resting blood pressure and renal sympathetic nerve activity (RSNA). In addition direct recordings from single unit bulbospinal RVLM neurons revealed that kynurenic acid decreased the already elevated firing frequency of RVLM units from CHF but had not sham rats. Sham rats were those that had had the open chest surgery required for the coronary ligation CHF model without actually tying off the coronary artery. Sham and coronary ligated animals were studied 6-8 weeks after the ligation or sham surgery. The conclusions of the paper are that glutamate activing via both NMDA and non-NMDA (likely AMPA) receptors located on RVLM neurons contributes to elevations in resting RVLM neuronal firing and increased basal SNA in heart failure. Because antagonists were used it was not possible to determine whether the increase glutamate neurotransmission was due to increased input or a change in post-synaptic receptors or transduction mechanisms. Because unit recordings confirmed a glutamate senstive increase in resting firing frequency these data suggests that elevated SNA was due at least in part to increased firing of RVLM neurons rather than downstream changes at the level of the spinal cord or sympathetic ganglion. A prime region that could contribute to increase glutamatergic input is the paraventricular nucleus of the hypothalamus, a brain regions that has been extensively studied by this group in previous studies related to heart failure. Finally, the PVN is known to be overactive in CHF animals and it also has direct glutamatergic projections to the RVLM so it's logical to expect it is this connection that serves to drive excessive SNA in CHF. ~PJM