Ethanol selectively counteracts hypotension evoked by central I(1)-imidazoline but not alpha2-adrenergic receptor activation in spontaneously hypertensive rats.

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.