RVLM GLYCINE RECEPTORS MEDIATE GABAA AND GABABINDEPENDENT SYMPATHOINHIBITION FROM CVLM IN RATS. Cheryl M. Heesch,1 Jennifer D. Laiprasert,2 and Lyudmyla Kvochina1 Brain Res. 2006 December 13; 1125(1): 46–59

As we know, the neural regulation of blood pressure is carried through baroreflex which is always on and detects any blood pressure changes through the baroreceptors, and the rostral ventrolateral medulla (RVLM) is the most important brain region in the regulation of cardiovascular function through the baroreflex. In addition, the caudal ventrolateral medulla (CVLM) has been shown to have an important role in the modulation of the presympathetic RVLM neurons. Many studies have been done to prove that there is a tonically active GABAergic pathway from CVLM to RVLM, and the aim of this study is to evaluate the role of the RVLM GABAergic receptor subtypes and glycine receptors in mediating CVLM sympathoinhibition.

In this study, experiments were performed in 26 virgin female Sprague Dawley rats. This group of rats was divided into three groups each for different protocol. In protocol 1 and 2, the right nucleus tractus solitarius (NTS) was electrically lesioned to eliminate the effects of afferent baroreceptors input from the right side. The left CVLM and RVLM were functionally mapped based on the response to microinjection of GABA. In protocol 1, the changes in mean arterial blood pressure(MAP), heart rate(HR), and renal sympathetic nerve activity(RSNA) after microinjection of GABA in the left CVLM were measured before and after blockade of GABA A receptors in the left RVLM with bicuculline. The microinjection of GABA in the left CVLM before GABA receptors blockade resulted in significant increase in MAP and RSNA. After 10 minutes, GABA A receptor antagonist was microinjected in the left RVLM which produced an expected increase in both MAP and RSNA .Within 2 minutes, microinjection of GABA in the CVLM produced further increase in MAP and RSNA which indicated that there is a source of inhibition from the CVLM is not mediated by GABA A receptors in the RVLM. Based on that, the investigators of this study hypothesized that RVLM GABA B receptors might contribute to both tonic baroreflex independent sympahtoinhibition and the remaining CVLM sympathoinhibitory influence after RVLM GABA A receptors blockade. In protocol 2, they tested this hypothesis by measuring MAP, HR and RSNA responses to microinjection of GABA in the left CVLM before and after blockade of GABA A and GABA B receptors in the left RVLM. Following the combined GABA antagonists microinjection, the pressor response to inhibition of the CVLM was decreased while MAP and RSNA responses persisted, suggesting that GABA B receptors do not make a major contribution to GABAergic inhibition from CVLM to RVLM.

Although in protocol 1 and 2  NTS lesion on the right side eliminated the effect of right baroreflex, they considered that the combination of minor effects of baroreceptors from the left NTS to CVLM pathway and baroreflex independent inhibition from the left CVLM to the right RVLM could be accounted for residual responses  to inhibition of left  CVLM.  Therefore, in protocol 3, bilateral blockade of GABA A and GABA B receptors in the RVLM was performed and changes in MAP, HR and RSNA after microinjection of GABA in the CVLM were measured before and after bilateral microinjection of the combined GABA antagonists.  The inhibition of CVLM after bilateral blockade of RVLM GABA receptors resulted in increased pressor response. In addition, glycine receptors blockade was evaluated in the presence of bilateral GABA A and GABA B receptors blockade to determine if RVLM glycine receptors contribute to the remaining inhibitory influence of the CVLM. They found that inhibition of glycine receptors resulted in elimination of the increase of MAP and RSNA that had been observed after the inhibition of CVLM in the presence of RVLM GABA receptors blockade.

To sum up, following ipsilateral blockade of RVLM GABA A(protocol 1) , ipsilateral GABA A+GABA B receptors (protocol 2) in rats with contralateral NTS lesion and following bilateral blockade of the RVLM GABA A+GABA B receptors the pressor and sympathoexcitatory responses persisted. These results indicate that there is no significant contribution of GABA B receptors to tonic baroreflex independent GABAergic inhibition from the CVLM to the RVLM and no evidence for influences form contralateral CVLM. Moreover, glycine receptors mediate GABA A and GABA B independent inhibition from the CVLM to the RVLM.