Increased GABA(A) inhibition of the RVLM after hindlimb unloading in rats.
Attenuated baroreflex-mediated increases in renal sympathetic nerve activity (RSNA) in hindlimb unloaded (HU) rats apparently are due to changes within the central nervous system. We hypothesized that GABA(A) receptor-mediated inhibition of the rostral ventrolateral medulla (RVLM) is increased after hindlimb unloading. Responses to bilateral microinjection of the GABA(A) antagonist (-)-bicuculline methiodide (BIC) into the RVLM were examined before and during caudal ventrolateral medulla (CVLM) inhibition in Inactin-anesthetized control and HU rats. Increases in mean arterial pressure (MAP), heart rate (HR), and RSNA in response to BIC in the RVLM were significantly enhanced in HU rats. Responses to bilateral CVLM blockade were not different. When remaining GABA(A) inhibition in the RVLM was blocked by BIC during CVLM inhibition, the additional increases in MAP and RSNA were significantly greater in HU rats. These data indicate that GABA(A) receptor-mediated inhibition of RVLM neurons is augmented after hindlimb unloading. Effects of input from the CVLM were unaltered. Thus, after cardiovascular deconditioning in rodents, the attenuated increase in sympathetic nerve activity in response to hypotension is associated with greater GABA(A) receptor-mediated inhibition of RVLM neurons originating at least in part from sources other than the CVLM.
Department of Veterinary Biomedical Sciences, Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri 65211, USA.
Julia A
JA
Moffitt
Cheryl M
CM
Heesch
Eileen M
EM
Hasser
D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists; D018698:Glutamic Acid / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D019417:Hindlimb Suspension / Q000502:physiology*; D007668:Kidney / Q000294:innervation; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D018474:Weightlessness Simulation
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D018698:Glutamic Acid; C017069:bicuculline methiodide; D001640:Bicuculline
NASA Discipline Cardiopulmonary; Non-NASA Center