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Heart failure‐induced changes in rostral ventral lateral medulla neurotransmitter receptor mRNA expression
Author(s) -
Helwig Bryan Glen,
Craig Robin A,
Fels Richard J,
Musch Timothy I,
Kenney Michael J
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1269-b
Subject(s) - rostral ventrolateral medulla , gabaa receptor , medicine , endocrinology , neurotransmitter , glutamate receptor , nmda receptor , brainstem , inhibitory postsynaptic potential , chemistry , receptor , excitatory postsynaptic potential , biology , central nervous system , medulla oblongata
Activation of the sympathetic nervous system occurs in heart failure (HF) and in response to acute bouts of hyperthermia. However, our previous work has demonstrated that rats with HF display attenuated sympathetic nerve discharge (SND) responses to an acute bout of hyperthermia and that SND responses to hyperthermia are mediated via brainstem neural circuits. Despite this, HF‐induced changes in excitatory (NMDA) and inhibitory (GABA) neurotransmitter systems within brainstem nuclei are not well understood. The rostral ventral lateral medulla (RVLM) has substantial sympathetic efferent projections to the intermediolateral column of spinal cord. Thus, we hypothesized that the RVLM of rats with HF may be characterized by altered expression of NMDA and GABA A receptor subunits. Using real‐time PCR analysis we compared NMDA and GABA A receptor subunit expression in the RVLM of sham‐operated and HF rats. Results of these preliminary studies indicate that in rats with HF mRNA expression of NMDA receptor subunits NR1, NR2A, and NR2B are increased between two and ten fold, whereas GABA A receptor subunits are increased two‐fold or less. These results suggest that although basal levels of GABA A receptor mRNA are only slightly elevated in rats with HF, expression of excitatory neurotransmitter receptor subunits in the RVLM are significantly increased. Neurotransmitter receptor subunit expression following an acute bout of hyperthermia continues to be determined, however, we hypothesize that GABA A and NMDA receptor subunit expression will be increased and decreased respectively in rats with HF, thereby contributing to the inability of HF rats to increase SND in response to a thermal challenge. Supported by NIH HL‐65346 and HL‐69755 (MJK) and AHA Postdoctoral Grant 0520105Z (BGH).