title: Evidence for the involvement of central I1 imidazoline receptor in ethanol counteraction of clonidine hypotension in spontaneously hypertensive rats.
abstract: Our previous studies have shown that ethanol counteracts centrally mediated hypotensive responses to clonidine. In this study, we investigated the relative roles of central alpha2-adrenergic and I1 imidazoline receptors in the antagonistic ethanol-clonidine hemodynamic interaction. The effects of selective blockade of alpha2- or I1 receptor by 2-methoxyidazoxan and efaroxan, respectively, on the blood pressure and heart rate responses to clonidine and subsequent ethanol administration were evaluated in conscious spontaneously hypertensive rats. Intracisternal administration of clonidine (1.5 microg/kg) produced significant (30 mm Hg; p < 0.05) and sustained (at least 60 min) decreases in blood pressure and heart rate. Systemic ethanol (1 g/kg), administered 10 min after clonidine, counteracted the hypotensive response and restored blood pressure to the preclonidine levels. Treatment with 2-methoxyidazoxan (0.16 microg/kg, intracisternal) or efaroxan (0.45 microg/kg, intracisternal) produced similar attenuation of the hypotensive and bradycardic responses to clonidine. The ability of ethanol to counteract the hypotensive action of clonidine was significantly (p < 0.05) attenuated in rats pretreated with efaroxan. The pressor response to ethanol lasted only 10 min compared with at least 60 min in the absence of efaroxan. In contrast, ethanol counteraction of clonidine-evoked hypotension was not altered when alpha2-adrenoceptors were blocked by 2-methoxyidazoxan. These findings suggest that centrally mediated hypotensive and bradycardic effects of clonidine in conscious spontaneously hypertensive rats involve activation of both alpha2-adrenergic and I1 imidazoline receptors. Furthermore, the findings suggest the dependence of a fully expressed ethanol counteraction of the hypotensive action of clonidine on functional I1 receptor within the central nervous system.
authors.affiliation: Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: El-Mas
authors.forename: A A
authors.initials: AA
authors.lastname: Abdel-Rahman
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002404:Catheterization; D003000:Clonidine / Q000494:pharmacology*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D019329:Idazoxan / Q000031:analogs & derivatives* / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D054755:Imidazoline Receptors; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; C410887:imidazoline I1 receptors; D000431:Ethanol; C058525:2-methoxyidazoxan; C062597:efaroxan; D003000:Clonidine; D019329:Idazoxan