Ethanol counteraction of clonidine-evoked inhibition of norepinephrine release in rostral ventrolateral medulla of rats.
Previous studies from our laboratory demonstrated an antagonistic hemodynamic interaction between ethanol and clonidine in conscious and in urethane-anesthetized rats. The present study tested the hypothesis that ethanol produces its effect by counteracting clonidine-evoked inhibition of norepinephrine (NE) release at its major site of action, the rostral ventrolateral medulla (RVLM). In vivo electrochemical measurement of real-time changes in NE level in the RVLM of urethane-anesthetized Sprague-Dawley rats was made along with blood pressure and heart rate. Clonidine (30 microg/kg, i.v.) produced significant decreases (p < 0.05) in NE electrochemical signal and blood pressure. Ethanol (1 g/kg, i.v.) administered 10 min after clonidine significantly (p < 0.05) increased NE signal and counteracted clonidine-evoked hypotension. Equal volume of saline had no effect on NE signal in the RVLM nor on the hypotensive response to clonidine. Pretreatment with the same dose of ethanol (1 g/kg) caused slight increases in RVLM NE level and in blood pressure, but did not influence the electrochemical and blood pressure responses to clonidine; clonidine (30 microg/kg) administration 10 min after ethanol resulted in significant (p < 0.05) decreases in NE signal and blood pressure. These findings suggest that: (i) ethanol counteraction of the hypotensive action of clonidine involves, at least in part, opposite effects on central pathways that use NE as a neurotransmitter; (ii) the RVLM represents a possible site for the adverse hemodynamic interaction between ethanol and clonidine; and (iii) ethanol-evoked increase in RVLM NE, which correlates with its pressor effect, is much enhanced when RVLM NE level is reduced by clonidine.
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina 27858-4354, USA.
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Abdel-Rahman
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001931:Brain Mapping; D003000:Clonidine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004347:Drug Interactions; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D009433:Neural Inhibition / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000431:Ethanol; D003000:Clonidine; D009638:Norepinephrine