GABAB receptor-mediated mechanisms in the RVLM studied by microinjections of two GABAB receptor antagonists

Abstract

The cardiovascular effects of microinjections of two gamma-aminobutyric acid (GABA) antagonists specifically acting on GABAB receptors, 2-hydroxy-saclofen (2-OH-S) and CGP-35348, into vasopressor sites of rostral ventrolateral medulla (RVLM) were studied in rats anesthetized with urethan. Bilateral microinjection of 2-OH-S induced significant increases in mean arterial pressure (MAP) and heart rate (HR) in 21 of 26 RVLM vasopressor sites (81%); average increases obtained in the 26 sites studied were +25.2 +/- 3.0 mmHg and +12.7 +/- 2.1 beats/min. Bilateral microinjection of CGP-35348 induced significant increases in MAP and HR in 10 of 12 RVLM sites (83%). Average increases in the 12 sites studied were +27.6 +/- 3.9 mmHg and +14.6 +/- 2.5 beats/min. Sixteen rats received unilateral electrolytic lesions of one RVLM. Microinjections of either 2-OH-S or CGP-35348 into vasopressor sites within the intact RVLM significantly antagonized the depressor responses observed after injections of baclofen (20 pmol) into the same sites, whereas both GABAB antagonists did not affect the depressor response induced by microinjection of muscimol (5 pmol). These results suggest a tonic inhibitory mechanism within the RVLM mediated by GABAB receptors involved in central cardiovascular regulation.

Urethane inhibits the GABAergic neurotransmission in the nucleus of the solitary tract of rat brain stem slices

“…However, in the same animals, the fall in blood pressure was greater after urethane anesthesia (15). Either GABA A receptor antagonists (bicuculline) or GABA B receptor antagonists (2-hydroxysaclofen or CGP-35348) microinjected in the RVLM produced a pressor response in urethane-anesthetized rats (1,5), suggesting that, at least in the RVLM, urethane is not producing inhibition of the tonic activity of GABAergic neurons projecting to this region. However, no experiments with the use of patch-clamp recordings were performed to explore the effect of urethane on RVLM neurons.…”

Increased GABAB Receptor Subtype Expression in the Nucleus of the Solitary Tract of the Spontaneously Hypertensive Rat

“…The observed increase in B1a expression in the VLM of SHR is interesting, as there is evidence that GABA B receptors may have a function in blood pressure regulation by inhibiting the activity of bulbospinal sympathetic premotor neurones of the rostral VLM (Amano and Kubo 1993;Avanzino et al 1994;Li and Guyenet 1995). In a previous immunohistochemical study, it was found that 95% of the C1 catecholamine neurones of the rostral VLM, believed to have an important role in blood pressure regulation (Guyenet 2006), expressed B1 subtype immunoreactivity and 86% expressed B2 immunoreactivity (Burman et al 2003).…”

RETRACTION: Mechanisms Underlying the Renoprotective Effect of GABA against Ischemia/Reperfusion-Induced Renal Injury in Rats

“…The paraventricular nucleus and the rostral ventrolateral medulla are known to be responsible for controlling the sympathetic outflow (Coote, 2005;Tjen-A-Looi et al, 2009). The microinjection of GABA or GABA receptor agonist into the rostral ventrolateral medulla or paraventricular nucleus decreased blood pressure by inhibiting sympathetic nerve activity (Avanzino et al, 1994;Li and Pan, 2007). Durgam et al (1999) reported that the microinjection of the GABA receptor agonist into the nucleus of the solitary tract, which is known to be central regulator for baroreflex, increased blood pressure by enhancing the sympathetic outflow.…”