Previous studies from our laboratory showed that
ethanol counteracts hypotensive responses to
clonidine in spontaneously hypertensive rats. This study investigated whether this effect of
ethanol involves interaction with central alpha2-adrenoceptors or I(1)-imidazoline receptors or both. The effects of
ethanol (0.5 or 1 g/kg, i.v.) or an equal volume of saline on hypotensive and bradycardic responses to
clonidine (mixed alpha2-
adrenoceptor/I(1)-
imidazoline receptor agonist),
rilmenidine (selective I(1)-
imidazoline receptor agonist), or
alpha-methylnorepinephrine (selective alpha2-
adrenoceptor agonist) were studied in conscious spontaneously hypertensive rats. Intracisternal administration of
clonidine (0.5 microg),
rilmenidine (25 microg), or
alpha-methylnorepinephrine (4 microg) elicited similar decreases in mean arterial pressure (MAP; 25-30 mm Hg) that lasted > or =60 min. Subsequent administration of
ethanol (0.5 and 1 g/kg, i.v.) counteracted the hypotensive effect of
clonidine in a dose-related manner.
Ethanol (1 g/kg) increased the blood pressure to levels similar to baseline (preclonidine) levels, and blood pressure remained significantly (p < 0.05) higher compared with the corresponding values in saline-treated rats. Similarly,
ethanol (0.5 and 1 g/kg, i.v.) dose-dependently counteracted the hypotensive effect of
rilmenidine. The antagonizing effects of
ethanol on
hypotension evoked by
clonidine and
rilmenidine were comparable in terms of both magnitude and duration. In contrast,
ethanol (0.5 or 1 g/kg) had no effect on
hypotension evoked by
alpha-methylnorepinephrine. Except for a brief increase in blood pressure by
ethanol (1 g/kg) at 5 min, blood pressure values obtained in
alpha-methylnorepinephrine-treated rats receiving any of the two doses of
ethanol were similar to postsaline values.
Ethanol had no effect on bradycardic responses to any of the three hypotensive agents. Blood
ethanol concentrations were similar regardless of the
antihypertensive drug used. We concluded that the adverse hemodynamic effect of
ethanol on centrally mediated hypotensive responses depends on the types of receptors involved in the elicitation of this response. That
ethanol counteracts decreases in blood pressure evoked by
clonidine and
rilmenidine but not by
alpha-methylnorepinephrine suggests an interaction between
ethanol and central pathways involved in I(1)-imidazoline receptor-mediated
hypotension.