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.