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) clonidine, 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 micrograms/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 group. Blood ethanol concentration was similar in the presence or absence of clonidine (5.5 +/- 1.9 versus 6.5 +/- 3 mmol/L).(ABSTRACT TRUNCATED AT 250 WORDS)
Abdel-Rahman
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Department of Pharmacology, East Carolina University School of Medicine, Greenville, NC 27858.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000503:physiopathology*; D003000:Clonidine / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D000431:Ethanol / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*
D000431:Ethanol; D003000:Clonidine