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Effect of Ethanol on Reductions in Norepinephrine Electrochemical Signal in the Rostral Ventrolateral Medulla and Hypotension Elicited by I 1 ‐Receptor Activation in Spontaneously Hypertensive Rats
Author(s) -
Mao Limin,
Li Guichu,
AbdelRahman Abdel A.
Publication year - 2003
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1097/01.alc.0000086062.95225.0c
Subject(s) - rostral ventrolateral medulla , microdialysis , rilmenidine , clonidine , imidazoline receptor , chemistry , norepinephrine , endocrinology , medicine , pharmacology , in vivo , blood pressure , heart rate , agonist , receptor , central nervous system , biology , dopamine , microbiology and biotechnology
Background: The mechanism of the antagonistic hemodynamic interaction between ethanol and centrally acting sympatholytics is not known. In this study, we tested the hypothesis that the imidazoline (I 1 )‐receptor modulation of norepinephrine (NE) release within the rostral ventrolateral medulla (RVLM) plays a pivotal role in this clinically relevant hemodynamic interaction. Method: In anesthetized spontaneously hypertensive rats, the effects of centrally acting sympatholytics on RVLM NE electrochemical signal were investigated by in vivo electrochemistry along with cardiovascular responses in the absence and presence of ethanol. In vivo microdialysis in conscious spontaneously hypertensive rats was used to confirm the electrochemical findings. Results: Clonidine (30 μg/kg, intravenously) or rilmenidine (400, 600, or 800 μg/kg) significantly reduced RVLM NE electrochemical signal (index of neuronal activity) and mean arterial pressure; rilmenidine effects were dose‐related, and ethanol (1 g/kg) counteracted these responses. Ethanol (1 g/kg) pretreatment increased both RVLM NE electrochemical signal and blood pressure but did not influence the reductions in both variables elicited by subsequently administered clonidine. The α 2 ‐adrenergic antagonist 2‐methoxyidazoxan (30 μg/kg) counteracted rilmenidine (800 μg/kg)‐evoked responses. In vivo microdialysis in conscious spontaneously hypertensive rats confirmed the electrochemical findings since clonidine‐ (30 μg/kg, intravenously) evoked reductions in RVLM NE and the associated hypotension were counteracted by ethanol (1 g/kg). Conclusions: (1) Ethanol counteracts centrally mediated hypotension, at least in part, by increasing RVLM NE; (2) the interaction involves the I 1 receptor modulation of RVLM neuronal activity; (3) the α 2 ‐adrenergic receptor contributes to the electrochemical and cardiovascular effects of high doses of rilmenidine, and (4) the RVLM is a neuroanatomical target for systemically administered ethanol.