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GABA A AND GABA B RECEPTOR‐MEDIATED INHIBITION OF SYMPATHETIC OUTFLOW IN THE PARAVENTRICULAR NUCLEUS IS BLUNTED IN CHRONIC HEART FAILURE
Author(s) -
Wang RenJun,
Zeng QingHua,
Wang WeiZhong,
Wang Wei
Publication year - 2009
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2008.05101.x
Subject(s) - medicine , endocrinology , bicuculline , muscimol , microinjection , agonist , gabaa receptor , receptor , chemistry , receptor antagonist , antagonist
SUMMARY1 Alterations in the paraventricular nucleus (PVN) are reported to be involved in sympathetic overactivity in chronic heart failure (CHF). Inhibitory inputs into the PVN contribute to sympathetic outflow. The aim of the present study was to comparatively determine the role of GABA mechanisms in the PVN in the tonic control of cardiovascular activity in anaesthetized sham and CHF rats. 2 The CHF model was induced by coronary artery ligation. Unilateral microinjection of the GABA A receptor agonist muscimol (0.1–0.8 nmol/200 nL) or the GABA B receptor agonist baclofen (0.25–2.0 nmol/200 nL) into the PVN produced similar, dose‐dependent reductions in arterial pressure (AP), heart rate (HR) and renal sympathetic nerve activity (RSNA). This response was significantly blunted in CHF rats. In contrast, microinjection of the GABA A receptor antagonist bicuculline (25–200 pmol/200 nL) or the GABA B receptor antagonist CGP35348 (0.25–2.0 nmol/200 nL) into the PVN caused larger, dose‐dependent increases in AP, HR and RSNA in sham than in CHF rats. 3 Polymerase chain reaction data showed that mRNA expression levels of the GABA A receptor α 1 ‐subunit and of the GABA B1(a) and GABA B1(b) receptor subtypes in the PVN were significantly lower in CHF than in sham rats. 4 The results of the present study suggest that the tonic inhibition mediated by both GABA A and GABA B receptors in the PVN on sympathetic outflow is blunted in CHF, which may be an important mechanism responsible for sympathetic hyperactivity in CHF.