Ethanol abolishes clonidine-induced impairment of baroreflex control of heart rate in conscious rats.
Our previous studies showed that the ability of ethanol or clonidine 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 i.v.) 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 microg/kg, i.v.) 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, i.v.) 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 clonidine 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.
El-Mas
M M
MM
Department of Pharmacology, Faculty of Pharmacy, University of Alexandria, Egypt. mahelm@hotmail.com
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000139:chemically induced / Q000517:prevention & control; D003000:Clonidine / Q000494:pharmacology*; D003714:Denervation / Q000009:adverse effects; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D011311:Pressoreceptors / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D000959:Antihypertensive Agents; D000431:Ethanol; D003000:Clonidine