ALCOHOL ABOLISHES THE HYPOTENSIVE EFFECT OF CLONIDINE IN SPONTANEOUSLY HYPERTENSIVE RATS

This study tested the hypothesis that concurrent ethanol administratio n attenuates the hypotensive effect of clonidine. Four groups of spont aneously 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 fr om similar baseline systolic blood pressures, the blood pressure of th e control group increased 10 to 15 mm Hg over the 13-week treatment pe riod. A similar rise in systolic blood pressure occurred in ethanol-tr eated rats despite a drastic (40% to 50%, P<.05) reduction in fluid in take. Clonidine (300 mu g/kg per day) caused a smaller and shorter red uction in fluid intake. The fluid intake of the combined treatment gro up was similar to that of the ethanol group. Either treatment caused a significant and additive reduction in body weight gain. Treatment-rel ated mortality (20%) occurred only in the combined treatment group by the 12th week. Clonidine elicited a slowly developing hypotensive resp onse (P<.05) that started 2 to 3 weeks after treatment was initiated a nd lasted throughout the treatment period. Ethanol abolished the hypot ensive effect of clonidine and resulted in blood pressure values that were not significantly different from those of the control or the etha nol groups. Blood ethanol concentration was similar in the presence or absence of clonidine (5.5+/-1.9 versus 6.5+/-3 mmol/L). We investigat ed whether long-term ethanol administration attenuates the hypotensive response elicited by centrally administered clonidine. The dose-respo nse curve depicting the hypotensive responses to intracisternal clonid ine in the ethanol-treated group was significantly shifted upward comp ared with that of the control group. We conclude the following: (1) et hanol coadministration abolishes the hypotensive effect of clonidine i n conscious SHR; (2) ethanol-induced reduction in fluid intake whether given alone or in combination with clonidine may have masked its pres sor effect; (3) ethanol and clonidine exert an additive inhibitory eff ect on body weight gain; and (4) ethanol adversely influences the acti vity of the central pathways involved in the hypotensive response to c lonidine.