ALCOHOL ABOLISHES THE HYPOTENSIVE EFFECT OF CLONIDINE IN SPONTANEOUSLY HYPERTENSIVE RATS

This study tested the hypothesis that concurrent ethanol administration attenuates the hypotensive effect of clonidine. Four groups of spontaneously hypertensive rats matched for baseline systolic pressure and body weight were randomly assigned the following treatments: (1) water (control), (2) ethanol, (3) cionidine, and (4) ethanol plus clonidine for 13 weeks. Ethanol was provided in the drinking water as 5% for 1 week. 10% for the next 2 weeks, and 20% from week 4 to 13. Starting from similar baseline systolic blood pressures, the blood pressure of the control group increased 10 to 15 mm Hg over the 13-week treatment period. A similar rise in systolic blood pressure occurred in ethanol-treated rats despite a drastic (40% to 50%, P<.05) reduction in fluid intake. Clonidine (300 mu g/kg per day) caused a smaller and shorter reduction in fluid intake. The fluid intake of the combined treatment group was similar to that of the ethanol group. Either treatment caused a significant and additive reduction in body weight gain. Treatment-related mortality (20%) occurred only in the combined treatment group by the 12th week. Clonidine elicited a slowly developing hypotensive response (P<.05) that started 2 to 3 weeks after treatment was initiated and lasted throughout the treatment period. Ethanol abolished the hypotensive effect of clonidine and resulted in blood pressure values that were not significantly different from those of the control or the ethanol groups. Blood ethanol concentration was similar in the presence or absence of clonidine (5.5+/-1.9 versus 6.5+/-3 mmol/L). We investigated whether long-term ethanol administration attenuates the hypotensive response elicited by centrally administered clonidine. The dose-response curve depicting the hypotensive responses to intracisternal clonidine in the ethanol-treated group was significantly shifted upward compared with that of the control group. We conclude the following: (1) ethanol coadministration abolishes the hypotensive effect of clonidine in conscious SHR; (2) ethanol-induced reduction in fluid intake whether given alone or in combination with clonidine may have masked its pressor effect; (3) ethanol and clonidine exert an additive inhibitory effect on body weight gain; and (4) ethanol adversely influences the activity of the central pathways involved in the hypotensive response to clonidine.