Abdel-Rahman A A
Department of Pharmacology, East Carolina University, School of Medicine, Greenville, NC 27858.
Hypertension. 1989 Nov;14(5):531-41. doi: 10.1161/01.hyp.14.5.531.
We studied the acute effect of ethanol on the hypotensive response to clonidine in conscious spontaneously hypertensive rats. When administered during the hypotensive response to clonidine, ethanol not only reversed the response but also caused a slight but significant short-lived pressor effect. The maximal hypotensive effect of graded doses of clonidine was significantly (p less than 0.05) attenuated by a dose of 1 g/kg ethanol, which resulted in a peak blood ethanol concentration of 54.2 +/- 6.3 mg/dl. The data strongly suggest the adverse effect of ethanol on the hypotensive response to clonidine is ethanol mediated and that their antagonistic interaction is both reversible and reproducible because: 1) an equal volume of saline had no effect on the hemodynamic responses to clonidine and 2) crossing over ethanol and saline treatments on days 2 and 3, which allowed longitudinal comparisons, showed that the effect of ethanol was similar both in naive rats (day 1) and in rats that were pre-exposed to ethanol (day 3). Whether this negative effect of ethanol also involves other antihypertensive agents that do not act primarily by a central nervous system mechanism was investigated. The same dose of ethanol had little or no effect on the hypotensive response to hydralazine, suggesting the negative effect of ethanol is selective to centrally acting antihypertensive agents. Although the mechanism by which ethanol reverses the hypotensive effect of clonidine is not known, it is possible that it involves an ethanol-evoked increase in plasma catecholamine levels, which are known to be decreased by clonidine. That ethanol did not reverse the hypotensive effect of hydralazine, which is also known to be associated with increased plasma catecholamine levels, supports this notion. The findings of the present study may explain, at least in part, why regular use of alcohol is associated with an inadequate control of blood pressure in treated hypertensive patients who are regular consumers of alcohol.
我们研究了乙醇对清醒自发性高血压大鼠可乐定降压反应的急性影响。在可乐定降压反应期间给予乙醇时，乙醇不仅会逆转该反应，还会引起轻微但显著的短暂升压效应。1g/kg乙醇剂量可显著（p<0.05）减弱不同剂量可乐定的最大降压效应，该剂量乙醇导致的血乙醇峰值浓度为54.2±6.3mg/dl。这些数据有力地表明，乙醇对可乐定降压反应的不良影响是由乙醇介导的，且它们的拮抗相互作用是可逆且可重复的，原因如下：1）等体积的生理盐水对可乐定的血流动力学反应无影响；2）在第2天和第3天交叉给予乙醇和生理盐水处理以进行纵向比较，结果显示乙醇在未接触过乙醇的大鼠（第1天）和预先接触过乙醇的大鼠（第3天）中的作用相似。我们还研究了乙醇的这种负面影响是否也涉及其他并非主要通过中枢神经系统机制起作用的抗高血压药物。相同剂量的乙醇对肼屈嗪的降压反应几乎没有影响，这表明乙醇的负面影响对中枢作用的抗高血压药物具有选择性。虽然乙醇逆转可乐定降压作用的机制尚不清楚，但有可能是它引起血浆儿茶酚胺水平升高，而可乐定已知会降低血浆儿茶酚胺水平。乙醇并未逆转肼屈嗪的降压作用，而肼屈嗪也已知与血浆儿茶酚胺水平升高有关，这支持了这一观点。本研究的结果可能至少部分解释了为什么经常饮酒的高血压患者在接受治疗时血压控制不佳。
