Ethanol-clonidine hemodynamic interaction in normotensive rats is modified by anesthesia

Abstract

Our previous findings have shown that ethanol attenuates the decreases in plasma norepinephrine (NE) levels, and blood pressure elicited by centrally acting antihypertensive drugs in spontaneously hypertensive rats (SHRs). The present study investigated whether this interaction can be influenced by baseline blood pressure (BP) and sought direct evidence to support the involvement of the SNS by recording the sympathetic neural activity (SNA) of the splanchnic nerve. The conscious aortic barodenervated (ABD) rat model was utilized because it exhibits greater hypotensive responses to clonidine compared with sham-operated (SO) rats. Although ABD and SO rats exhibited similar basal MAP (104 + 4 vs. 99 + 2 mm Hg), plasma NE levels were higher in conscious ABD rats (332 + 33 vs. 227 + 18 pg/ml). Clonidine (30 μg/kg, IV) elicited significantly greater decreases in mean arterial pressure (MAP; −20.0 + 2.1 vs. −10.4 + 0.8 mm Hg) and plasma NE (−194 + 26 vs. −50 + 11 pg/ml) in conscious ABD vs. SO rats. Ethanol (1 g/kg, IV) reversed clonidine-evoked decreases in BP and plasma NE levels, but the interaction was more prominent in ABD rats. To support the hypothesis that the interaction occurs within the CNS, the effect of ethanol was studied on clonidine-evoked decreases in preganglionic SNA and BP in anesthetized rats. In contrast to its effects in conscious rats, ethanol augmented both the hypotensive and sympathoinhibitory responses to clonidine in anesthetized rats. It is concluded that: a) an adverse ethanol-clonidine hemodynamic interaction occurs in conscious normotensive rats, b) anesthesia reverses ethanol-clonidine hemodynamic interaction, whereby ethanol enhances the hypotensive action of clonidine, and c) the SNS is directly involved in the interaction because whether the hypotensive action of clonidine was attenuated (conscious state) or enhanced (anesthetized state) by subsequent ethanol administration, a parallel change occurred in the SNS. Given the popularity of utilizing clonidine as a preanesthetic medication, the present findings may have clinical relevance.