Reversal by ethanol of the hypotensive effect of clonidine in conscious spontaneously hypertensive rats.

Abdel‐Rahman, Abdel A.

doi:10.1161/01.hyp.14.5.531

Cited by 23 publications

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“…However, unlike the clinical study, in which the effect of ethanol was investigated on the pooled hypotensive responses elicited by a variety of monotherapies and combined therapies, 13 the present investigation focused on the interaction between ethanol and clonidine, a prototype of centrally acting drugs. The present findings extend our previous findings with clonidine 1 and another centrally acting drug, guanabenz, 2 in which acutely administered ethanol attenuated the hypotensive response elicited by these drugs in conscious SHR. It was not clear from these previous studies whether such an adverse hemodynamic interaction will manifest when ethanol and clonidine are administered on a long-term basis.…”

Section: Discussionsupporting

confidence: 90%

“…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.…”

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confidence: 99%

“…Our previous findings argue against this view because alcohol attenuated the hypotensive responses elicited by centrally acting but not by peripherally acting drugs. 1 …”

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

Abdel‐Rahman

1994

Hypertension

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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...

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

Abdel‐Rahman

1994

Hypertension

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“…Peak blood alcohol levels after that dose of ethanol vary significantly: 7.2 ± 0.43 mM [13], 11.8 ± 1.4 mM [21], 15.9 ± 2.2 mM [22], and 18.3 ± 1.0 mM [23]. …”

Section: Methodsmentioning

confidence: 99%

Inhibition of Rat Muscle and Liver Phosphofructokinases by High Doses of Ethanol

Лелевич

Khrustalev²,

Barkovsky³

2013

Biochemistry Research International

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Activities of both rat muscle and liver phosphofructokinases are significantly inhibited after a single ethanol intake in the dose of 2.5 g per kg of body weight. This inhibitory effect is indirect, since ethanol in concentration (50 mM) close to that established after 2.5 g per kg of body weight intake cannot decrease their activities in vitro. Inhibition of liver phosphofructokinase activity after the 5.0 g per kg ethanol intake may be direct, since liver phosphofructokinase activity decreases in vitro when ethanol is added to supernatants of rat liver tissue in 100 mM concentration. According to the results of molecular docking, ethanol at high concentrations can be bound by adenine-binding pocket of the allosteric ADP-binding site of liver phosphofructokinase (Asp543, Phe308, Phe538, and Phe671) and its activation by ADP can be blocked by C2H5OH molecule. Direct inhibition of muscle phosphofructokinase activity, probably due to the binding of ethanol to the similar ADP-binding site, is possible when the concentration of ethanol (500 mM) is much higher than the level which can be established in living cells. So, inhibition of muscle phosphofructokinase activity after a single 5.0 g per kg intake is indirect and probably linked with the inhibition of the enzyme by elevated citrate and phosphoenolpyruvate levels.

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“…clonidine) but not peripherally mediated hypotension (e.g. hydralazine) (Abdel-Rahman, 1989). Because clonidine exhibits almost similar affinities at α 2 and I 1 receptors, subsequent studies investigated the hemodynamic interaction of ethanol with clonidine-related drugs with selective agonistic activity at either receptor site.…”

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Chronic ethanol attenuates centrally-mediated hypotension elicited via α2-adrenergic, but not I1-imidazoline, receptor activation in female rats

El‐Mas

Abdel‐Rahman

2009

Life Sciences

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Aims This study dealt with the effect of chronic ethanol administration on hemodynamic responses elicited by α2-adrenergic (α-methyldopa) or I1-imidazoline (rilmenidine) receptor activation in telemetered female rats. Main methods The effects of α-methyldopa or rilmenidine on blood pressure (BP), heart rate (HR) and their variability were investigated in rats that received liquid diet without or with ethanol (5% w/v) for 12 weeks. To evaluate the effect of each drug on cardiovascular autonomic control (BP and HR variability) in the absence or presence of ethanol, three time-domain indices of hemodynamic variability were measured: (i) standard deviation of mean arterial pressure (SDMAP), (ii) standard deviation of beat-to-beat intervals, and (iii) root mean square of successive differences in R-R intervals. Key findings In liquid diet-fed control rats, i.p. rilmenidine (600 μg/kg) or α-methyldopa (100 mg/kg) reduced BP along with decreases and increases, respectively, in HR. Both drugs had no effect on HR variability but reduced BP variability (SDMAP), suggesting a reduced vasomotor sympathetic tone. Ethanol feeding attenuated reductions in BP and SDMAP evoked by α-methyldopa but not by rilmenidine. Significance We conclude that chronic ethanol preferentially compromises α2- but not I1-receptor-mediated hypotension in female rats probably via modulation of vasomotor sympathetic activity. These findings highlight the adequacy of rilmenidine use to lower BP in hypertensive alcoholic females.

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Reversal by ethanol of the hypotensive effect of clonidine in conscious spontaneously hypertensive rats.

Cited by 23 publications

References 25 publications

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

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

Inhibition of Rat Muscle and Liver Phosphofructokinases by High Doses of Ethanol

Chronic ethanol attenuates centrally-mediated hypotension elicited via α2-adrenergic, but not I1-imidazoline, receptor activation in female rats

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