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Inhibition of Brainstem GABAergic Neurotransmission Plays A Causal Role in Central CB1R‐Evoked Pressor Response
Author(s) -
Ibrahim Badr Mostafa,
AbdelRahman Abdel A.
Publication year - 2011
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.25.1_supplement.1084.9
Subject(s) - rostral ventrolateral medulla , muscimol , chemistry , medicine , endocrinology , brainstem , gabaergic , am251 , catecholaminergic , norepinephrine , neurotransmission , agonist , medulla oblongata , catecholamine , central nervous system , receptor , dopamine , cannabinoid receptor
We have previously shown that central activation of CB 1 R (WIN55,212‐2) elicits pressor response in conscious rats along with enhancement of nNOS–derived NO generation within the rostral ventrolateral medulla (RVLM). Given the well‐established link between nNOS‐NO signaling and GABAergic transmission in cardiovascular regulatory areas, we hypothesized that inhibition of RVLM GABAergic transmission accounts for the central CB 1 R mediated pressor response. Intracisternal (i.c) administration of WIN55,212‐2 (15 μg/rat) in conscious freely moving rats elevated mean arterial pressure (MAP), reduced heart rate (HR) and increased plasma norepinephrine (NE) levels. Activation of brainstem GABA A receptor by muscimol (0.1 μg/rat, i.c) or blockade of CB 1 R by selective antagonist, AM251 (30 μg/rat, i.c) virtually abolished WIN55,212‐2 (15 μg/rat, i.c)‐evoked hemodynamic responses. Additionally, we utilized c‐Fos to indirectly measure the activity of catecholaminergic (tyrosine hydroxylase immunoreactivity, TH‐ir) and nitroxidergic (nNOS‐ir) neurons within the RVLM following the activation of central CB 1 R in presence or absence of AM251 or muscimol. WIN55,212‐2 (15 μg/rat, i.c)‐evoked pressor response was associated with significant ( P < 0.05) increases in the percentage of TH‐ir and nNOS‐ir neurons expressing c‐Fos. Further, AM251 or muscimol pretreatment mitigated the central WIN55,212‐2 evoked pressor response and the increases in RVLM‐catecholaminergic and nitroxidergic neuronal activity. Together, these findings suggest a causal role for NO mediated inhibition of GABAergic transmission in the RVLM in the central CB 1 R‐evoked pressor response.