El-Mas M M, Abdel-Rahman A A
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, North Carolina, USA.
J Cardiovasc Pharmacol. 2001 Sep;38(3):417-26. doi: 10.1097/00005344-200109000-00010.
Our previous studies have shown that ethanol counteracts centrally mediated hypotensive responses to clonidine. In this study, we investigated the relative roles of central alpha2-adrenergic and I1 imidazoline receptors in the antagonistic ethanol-clonidine hemodynamic interaction. The effects of selective blockade of alpha2- or I1 receptor by 2-methoxyidazoxan and efaroxan, respectively, on the blood pressure and heart rate responses to clonidine and subsequent ethanol administration were evaluated in conscious spontaneously hypertensive rats. Intracisternal administration of clonidine (1.5 microg/kg) produced significant (30 mm Hg; p < 0.05) and sustained (at least 60 min) decreases in blood pressure and heart rate. Systemic ethanol (1 g/kg), administered 10 min after clonidine, counteracted the hypotensive response and restored blood pressure to the preclonidine levels. Treatment with 2-methoxyidazoxan (0.16 microg/kg, intracisternal) or efaroxan (0.45 microg/kg, intracisternal) produced similar attenuation of the hypotensive and bradycardic responses to clonidine. The ability of ethanol to counteract the hypotensive action of clonidine was significantly (p < 0.05) attenuated in rats pretreated with efaroxan. The pressor response to ethanol lasted only 10 min compared with at least 60 min in the absence of efaroxan. In contrast, ethanol counteraction of clonidine-evoked hypotension was not altered when alpha2-adrenoceptors were blocked by 2-methoxyidazoxan. These findings suggest that centrally mediated hypotensive and bradycardic effects of clonidine in conscious spontaneously hypertensive rats involve activation of both alpha2-adrenergic and I1 imidazoline receptors. Furthermore, the findings suggest the dependence of a fully expressed ethanol counteraction of the hypotensive action of clonidine on functional I1 receptor within the central nervous system.
我们之前的研究表明，乙醇可对抗可乐定引起的中枢介导的降压反应。在本研究中，我们调查了中枢α2-肾上腺素能受体和I1咪唑啉受体在乙醇-可乐定血流动力学拮抗相互作用中的相对作用。分别用2-甲氧基咪唑克生和依酚氯铵选择性阻断α2或I1受体，评估其对清醒自发性高血压大鼠对可乐定及随后乙醇给药的血压和心率反应的影响。脑池内注射可乐定（1.5微克/千克）可使血压和心率显著（30毫米汞柱；p<0.05）且持续（至少60分钟）下降。可乐定注射10分钟后给予全身乙醇（1克/千克），可对抗降压反应并使血压恢复到可乐定给药前水平。用2-甲氧基咪唑克生（0.16微克/千克，脑池内注射）或依酚氯铵（0.45微克/千克，脑池内注射）治疗，对可乐定引起的降压和心动过缓反应有类似的减弱作用。在预先用依酚氯铵处理的大鼠中，乙醇对抗可乐定降压作用的能力显著（p<0.05）减弱。与未用依酚氯铵时至少60分钟相比，乙醇的升压反应仅持续10分钟。相反，当α2-肾上腺素能受体被2-甲氧基咪唑克生阻断时，乙醇对可乐定诱发低血压的对抗作用未改变。这些发现表明，在清醒自发性高血压大鼠中，可乐定的中枢介导的降压和心动过缓作用涉及α2-肾上腺素能受体和I1咪唑啉受体的激活。此外，这些发现表明，乙醇对可乐定降压作用的充分表达的对抗作用依赖于中枢神经系统内功能性I1受体。
