Alcohol abolishes the hypotensive effect of clonidine in spontaneously hypertensive rats.

Abstract

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 p.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 I n a previous study we showed that short-term ethanol administration elicited an immediate reversal of the hypotensive response to clonidine in conscious, unrestrained spontaneously hypertensive rats (SHR).1 This adverse effect of ethanol seems to be targeted against centrally acting hypotensive drugs. In support of this view is the finding that a similar hemodynamic interaction occurs between ethanol and another centrally acting drug, guanabenz.2 The hemodynamic interaction is dose related 2 and involves ethanol doses that are likely to be consumed clinically and lead to blood ethanol concentrations compatible with low to moderate intoxication. Interestingly, in the dose range used in these studies, 2 This latter effect may explain the immediate reversal by ethanol of the hypotensive response of centrally acting drugs that is the consequence of an inhibition of central sympathetic tone. From the Department of Pharmacology, East Carolina University School of Medicine, Greenville, NC.Correspondence to Abdel A. Abdel-Rahman, PhD, Department of Pharmacology, East Carolina University School of Medicine, Greenville, NC 27858.© 1994 American Heart Association, Inc.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 upwar...

Effects of Chronic Ethanol Feeding on Clonidine-Evoked Reductions in Blood Pressure, Heart Rate, and Their Variability: Time-Domain Analyses

“…In effect, clonidine increased heart rate variability indices (SDRR and rMSSD) in rats receiving the higher concentration of ethanol. Second, the hypotensive response to intracisternally administered clonidine was attenuated in ethanol chronically fed SHRs whose baseline blood pressure was similar to that of control SHRs (Abdel-Rahman, 1994), suggesting that differences in baseline blood pressure in the present study may not account for the attenuated clonidine hypotension in ethanol-fed rats. Third, the antagonistic ethanol-clonidine hemodynamic interaction has been demonstrated in arterial barodenervated rats (El-Mas et al, 1994b; El-Mas and Abdel-Rahman, 1997) whose baseline blood pressure was less than that seen in ethanol-fed rats in the present study.…”

“…This clinically important phenomenon has been demonstrated in experimental animals in our previous reports, which showed that ethanol, administered acutely or chronically, counteracts the hypotensive effect of clonidine and related antihypertensive agents (Abdel-Rahman et al, 1992;Abdel-Rahman, 1994;El-Mas et al, 1994b). In contrast, peripherally mediated hypotensive responses elicited by hydralazine, nitroprusside, or hexamethonium are not influenced by ethanol (AbdelRahman et al, 1992;El-Mas and Abdel-Rahman, 1999).…”

“…Although ethanol counteraction of clonidine-evoked hypotension has been documented (Abdel-Rahman, 1994;El-Mas et al, 1994b), whether ethanol adversely affects the beneficial actions of clonidine on blood pressure and heart rate oscillations has not been investigated. This possibility was investigated in the present study by evaluating the effect of chronic ethanol feeding on clonidine-evoked acute changes in blood pressure, heart rate, and their variability in radiotelemetered SHRs.…”

Alveolar fluid reabsorption is increased in rats with compensated heart failure

“…Cardiac output was measured by Cardiomax (Columbus Instruments, Columbus, OH) interfaced with a computer, based on the thermodilution technique with a thermocouple in the thoracic aorta via the carotid artery (2,19).…”

Physio-pathological effects of alcohol on the cardiovascular system: its role in hypertension and cardiovascular disease

“…Abdel-Rahman 85 reported that the BP increase was not different between ethanol-fed (5-20% in drinking water) spontaneously hypertensive (SH) rats and control SH rats during a 13-week observation period. The depressor effect of clonidine, however, was reduced in the ethanol-fed SH rats, suggesting a change in the neural regulation of BP.…”