RVLM glycine receptors mediate GABAA and GABAB independent sympathoinhibition from CVLM in rats

Abstract

The caudal ventrolateral medulla (CVLM) provides tonic inhibitory and also excitatory inputs to the rostral ventrolateral medulla (RVLM). These experiments evaluated the role of RVLM γ-amino butyric acid (GABA) receptor subtypes and glycine receptors in mediating CVLM sympathoinhibition. In Inactin anesthetized female rats, the CVLM and RVLM were functionally defined by pressor and depressor responses to microinjected GABA (500 pmol, 50 nl). Although reduced, pressor and sympathoexcitatory responses due to inhibition of the CVLM with GABA persisted following ipsilateral RVLM GABA A receptor blockade (bicuculline, BIC, 400 pmol, 100 nl; n=12) in rats with contralateral nucleus tractus solitarius (NTS) lesion. In the presence of either ipsilateral (+contralateral NTS lesion; n= 8) or bilateral (n=6) GABA A and GABA B receptor blockade of the RVLM (400 pmol BIC + 400 pmol CGP35348, 100 nl), inhibition of the CVLM still increased MAP and renal sympathetic nerve activity (RSNA). Thus neither GABA B receptors nor a contralateral CVLM to RVLM GABAergic pathway explains residual responses CVLM blockade. The addition of strychnine (300 pmol, 100 nl) to the RVLM eliminated responses to CVLM inhibition, suggesting that a GABA A and GABA B independent sympathoinhibitory influence from CVLM to RVLM is mediated by glycine receptors. Decreases in MAP and RSNA due to activation of the CVLM with glutamate (500 pmol, 50 nl) were reversed to increases in the presence of RVLM GABA A receptor blockade (n=7). Thus, a sympathoexcitatory pathway from the CVLM can be activated in the presence of RVLM GABA receptor blockade, but sympathoinhibitory influences from the CVLM predominate.

Pregnancy increases baroreflex-independent GABAergic inhibition of the RVLM in rats

“…Relative to calamus scriptorius, the stereotaxic coordinates for the RVLM were anteriorposterior ϭ 0.7 mm, medial-lateral ϭ 2.00 mm, and dorsal-ventral ϭ Ϫ3.6 -3.7 mm. These coordinates are within the range reported in other studies that used a similar method for positioning the rat in the stereotaxic frame and subsequently identified the RVLM (30,39,44). At the time of the experiment, the RVLM was functionally defined as the site that produced an increase in MAP Ն 15 mmHg and an increase in RSNA in response to microinjection of L-glutamate (10 mM, 30 nl).…”

Gene transfer of cystathionine β-synthase into RVLM increases hydrogen sulfide-mediated suppression of sympathetic outflow via KATP channel in normotensive rats

“…Sympathetic nerve activity was decreased by infusions of the NO donor sodium nitroprusside and GABA into the RVLM (14,18). In this study, microinjection of HA into the RVLM induced an increase in the MAP, HR, and RSNA.…”

Projection neurons of the vestibulo‐sympathetic reflex pathway

“…The RVLM provides the main excitatory input to preganglionic sympathetic neurons in the intermediolateral cell column of the spinal cord involved in the control of blood pressure (Blessing, 2004; Card et al, 2006; Dampney, 1994; Dampney et al, 1982; Guyenet, 2006; Lipski et al, 1995; Pilowsky and Goodchild, 2002; Reis, 1996; Reis et al, 1988; Ross et al, 1984a; Ross et al, 1984b; Sved et al, 2003; Willette et al, 1983). The CVLM, in contrast, provides both excitatory and inhibitory input to the RVLM (Blessing, 1988; Dampney et al, 2003; Guyenet, 1990; Heesch et al, 2006; Holstege, 1989; Jeske et al, 1995; Natarajan and Morrison, 2000; Pilowsky and Goodchild, 2002; Schreihofer et al, 2005; Stocker et al, 1997), as well as catecholaminergic projections to the hypothalamus and basal forebrain (Chan and Sawchenko, 1998; Cravo et al, 1991; Schreihofer and Guyenet, 2002). Accordingly, cells in the RVLM and CVLM have distinct and diverse roles, extending well beyond the basic circuitry of the baroreflex.…”