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.
Mao
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Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina 27858-4354, USA.
Abdel-Rahman
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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