NOVEL ROLE OF GLYCINE IN CONTROL OF SYMPATHETIC OUTFLOW

Abstract

The arterial baroreflex is one of the essential negative‐feedback mechanisms that compensates rapid changes in blood pressure (BP) through inhibition of presympathetic neurons in the rostral ventrolateral medulla (RVLM). There is general consensus that GABAergic projections originating from the caudal VLM (CVLM) provide the primary inhibitory input that controls the excitability of presympathetic RVLM neurons and sympathetic output. However, glycine, another inhibitory neurotransmitter, is also present in the RVLM. In anesthetized rats, we found that RVLM glycine played a critical role in arterial baroreflex function by controlling the time course of baroreflex mediated inhibition of renal sympathetic nerve activity. Blockade of glycine receptors in the RVLM, following an increase in BP, increased recovery of renal sympathetic nerve activity to baseline levels (5.1 ± 1.0 vs 11.7 ± 1.3 min, N=6, P<0.01) in comparison to control. In addition, tonic glycinergic inhibition of the RVLM was unmasked following blockade of output from the nucleus tractus solitaries and/or during disinhibition of the CVLM. Our whole‐cell, patch‐clamp recordings were obtained from brainstem slices containing presympathetic neurons in the RVLM labeled with PRV‐152. We confirmed that in steady state conditions GABAergic inhibition of RVLM neurons predominated and glycine contributed less than 25% of overall inhibition. In contrast, activation of the network produced saturation of GABAergic inhibition and glycinergic inhibition became prominent. Our findings demonstrated that blockade of glycine receptors in the RVLM decreased duration of baroreflex sympathoinhibition; increase of BP and activation of the network unmasked glycinergic inhibition of the RVLM; and release of glycine in the RVLM depended on the activity of presynaptic inhibitory inputs.Support or Funding InformationNational Institutes of Health R01 HL98602 (Cheryl M. Heesch) and HL122829 (Andrei V. Derbenev). Australian Research Council Future Fellowship FT170100363 and the National Health and Medical Research Council of Australia GNT 1079680 (Song T. Yao). High Blood Pressure Research Council of Australia, the Rebecca L Cooper Medical Foundation, and the Victorian Government through the Operational Infrastructure Scheme (Willian S. Korim).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.