Contrasting effects of urethane, ketamine, and thiopental anesthesia on ethanol-clonidine hemodynamic interaction.
In previous studies, we have shown that ethanol counteracts the hypotensive and sympathoinhibitory effects of clonidine in conscious rats but enhances these responses in alpha-chloralose anesthetized rats. This study investigated whether the latter finding pertains to other anesthetics that act by different mechanisms. The hemodynamic interaction between clonidine and ethanol was evaluated in conscious aortic barodenervated rats and in rats anesthetized with urethane, ketamine, or thiopental. The conscious aortic barodenervated rat was used because it exhibits a greater hypotensive response to clonidine compared with intact (sham-operated) rats. Starting from similar baseline values of blood pressure (BP) and heart rate, clonidine (30 micrograms/kg, iv) elicited similar decreases in BP in all groups of rats (conscious aortic barodenervated or anesthetized). Subsequent administration of ethanol (1 g/kg, iv) counteracted the hypotensive effect of clonidine in conscious aortic barodenervated rats and raised the BP to levels higher than the baseline (preclonidine) values. The pressor effect of ethanol persisted for at least 30 min. In contrast, preadministration of ethanol had no effect on the hypotensive effect of the subsequently administered clonidine. The antagonistic clonidine-ethanol hemodynamic interaction in conscious rats was not altered in urethane-anesthetized rats, both in terms of magnitude and duration. In ketamine-anesthetized rats, a short lasting (< 10 min) pressor effect of ethanol was observed. In contrast, ethanol augmented the hypotensive effect of clonidine in thiopental-anesthetized rats; the hypotensive effect of clonidine became slightly but significantly (p < 0.05) greater after ethanol compared with respective time control values. These findings suggest that the adverse hemodynamic effect of ethanol on centrally mediated hypotensive response is modified by different anesthetics. The antagonistic hemodynamic interaction, demonstrated in conscious rats, is replicated in urethane-anesthetized rats but weakened and reversed in ketamine- and thiopental-anesthetized rats, respectively. Therefore, urethane-anesthetized rats may be used in mechanistic studies on the antagonistic ethanol-clonidine hemodynamic interaction that cannot be undertaken, for technical reasons, in conscious rats.
el-Mas
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MM
Department of Pharmacology, Faculty of Pharmacy, Alexandria University, Egypt.
Abdel-Rahman
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AA
D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003000:Clonidine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004347:Drug Interactions; D000431:Ethanol / Q000493:pharmacokinetics / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013874:Thiopental / Q000494:pharmacology*; D014520:Urethane / Q000494:pharmacology*
D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D000959:Antihypertensive Agents; D014520:Urethane; D000431:Ethanol; D007649:Ketamine; D013874:Thiopental; D003000:Clonidine