Reversal by ethanol of the hypotensive effect of clonidine in conscious spontaneously hypertensive rats.
We studied the acute effect of ethanol on the hypotensive response to clonidine in conscious spontaneously hypertensive rats. When administered during the hypotensive response to clonidine, ethanol not only reversed the response but also caused a slight but significant short-lived pressor effect. The maximal hypotensive effect of graded doses of clonidine was significantly (p less than 0.05) attenuated by a dose of 1 g/kg ethanol, which resulted in a peak blood ethanol concentration of 54.2 +/- 6.3 mg/dl. The data strongly suggest the adverse effect of ethanol on the hypotensive response to clonidine is ethanol mediated and that their antagonistic interaction is both reversible and reproducible because: 1) an equal volume of saline had no effect on the hemodynamic responses to clonidine and 2) crossing over ethanol and saline treatments on days 2 and 3, which allowed longitudinal comparisons, showed that the effect of ethanol was similar both in naive rats (day 1) and in rats that were pre-exposed to ethanol (day 3). Whether this negative effect of ethanol also involves other antihypertensive agents that do not act primarily by a central nervous system mechanism was investigated. The same dose of ethanol had little or no effect on the hypotensive response to hydralazine, suggesting the negative effect of ethanol is selective to centrally acting antihypertensive agents. Although the mechanism by which ethanol reverses the hypotensive effect of clonidine is not known, it is possible that it involves an ethanol-evoked increase in plasma catecholamine levels, which are known to be decreased by clonidine. That ethanol did not reverse the hypotensive effect of hydralazine, which is also known to be associated with increased plasma catecholamine levels, supports this notion. The findings of the present study may explain, at least in part, why regular use of alcohol is associated with an inadequate control of blood pressure in treated hypertensive patients who are regular consumers of alcohol.
Abdel-Rahman
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Department of Pharmacology, East Carolina University, School of Medicine, Greenville, NC 27858.
D000818:Animals; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004347:Drug Interactions; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D008297:Male; D009994:Osmolar Concentration; D011311:Pressoreceptors / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D012018:Reflex / Q000502:physiology
D000959:Antihypertensive Agents; D006830:Hydralazine; D000431:Ethanol; D003000:Clonidine