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Ethanol abolishes clonidine-induced impairment of baroreflex control of heart rate in conscious rats

https://doi.org/10.1016/S0306-3623(98)00207-9Get rights and content

Abstract

Our previous studies showed that the ability of ethanol or cholidine to alter the baroreflex control of heart rate (baroreflex sensitivity, BRS) depends on the functional activity of aortic baroreflexes. In this study, we investigated the interaction between the two drugs on BRS in conscious rats with intact baroreflexes (shamoperated, SO) and after aortic baroreceptor denervation (ABD). The slope of the curve relating increments in mean arterial pressure induced by phenylephrine to corresponding reflex bradycardic responses was taken as an index of BRS. Ethanol (1 g/kg IV) significantly (p < 0.05) attenuated BRS in SO rats (−1.7 ± 0.13 versus −1.04 ± 0.15 beats/min/mm Hg) but not in ABD rats. Clonidine (30 μg/kg, IV) elicited significantly (p < 0.05) greater hypotensive responses in conscious ABD compared with SO rats. The BRS was not affected by clonidine administration in SO rats but showed significant (p < 0.05) reductions in ABD rats. Ethanol (1 g/kg, IV) had no effect on the hypotensive response to subsequently administered clonidine in ABD and SO rats; however, the effect of the two drugs on BRS was variable. In ABD rats, the BRS values before and after administration of ethanol and clondine were similar, suggesting that pretreatment with ethanol counteracted clonidine-evoked attenuation of BRS in this rat preparation. In SO rats, the ethanol–clonidine combination produced a significant (p < 0.05) decrease in BRS, similar to the effect of ethanol when administered alone. These data confirm earlier findings that the aortic baroreflex arc modulates the interaction of ethanol and clonidine with baroreflex function. Further, the ability of ethanol to abolish clonidine-induced attenuation of BRS in ABD rats may relate to the compound effects of the two drugs on neuronal pathways participating in the central processing of baroreflexes in these rats.

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Preparation of the rats

Male Wistar rats (300–360 g; High Institute of Public Health, Alexandria, Egypt) were used in the present study. For measurement of blood pressure, the method described in previous studies El-Mas and Abdel-Rahman 1992, El-Mas and Abdel-Rahman 1993a was adopted. Briefly, the rats were anesthetized with thiopental (50 mg/kg, IP). Catheters (polyethylene 50) were placed in the abdominal aorta and vena cava through the femoral artery and vein for measurement of blood pressure and IV administration

Acute and short-term effects of ABD on baseline MAP and HR

Section of the aortic depressor nerves while the rats were anesthetized with thiopental resulted in immediate and statistically significant (p < 0.05) increases in MAP (from 111 ± 4 to 138 ± 5 mmHg) and HR (from 391 ± 10 to 423 ± 9 beats/min). In SO rats, no significant change in either variable was demonstrated (data not shown). Administration of a test dose of phenylephrine (8 μg/kg) before and after aortic baroreceptor denervation or sham operation revealed that the pressor effect of

Discussion

The most important finding of the present study was that prior administration of ethanol (1 g/kg) abolished the depressant effect of subsequently administered clonidine on BRS in conscious ABD rats. That this effect of ethanol was not associated with any alteration in the hypotensive effect of clonidine may add further support to the dissociation between the hypotensive effect of clonidine and its interaction with baroreflex function. These findings may suggest a modulatory role for ethanol on

Acknowledgements

Supported by the Faculty of Pharmacy, University of Alexandria, Egypt.

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