GABA(A) and GABA(B) receptor-mediated inhibition of sympathetic outflow in the paraventricular nucleus is blunted in chronic heart failure.
1. 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 alpha(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.
Wang
Ren-Jun
RJ
Laboratory of Molecular and Cellular Physiology, School of Life Science, North-east Normal University, Changchun, China.
Zeng
Qing-Hua
QH
Wang
Wei-Zhong
WZ
Wang
Wei
W
D000320:Adrenergic Fibers / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D006333:Heart Failure / Q000473:pathology* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D008954:Models, Biological; D009118:Muscimol / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D018755:GABA Agonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D009118:Muscimol; D001418:Baclofen; D001640:Bicuculline