Chen B X, Myles J, Wilkerson R D
Department of Pharmacology, Medical College of Ohio, Toledo 43699-0008, USA.
J Cardiovasc Pharmacol. 1995 May;25(5):817-22. doi: 10.1097/00005344-199505000-00019.
We investigated the role of peripheral sympathetic neurons and the adrenal medulla in the cardiovascular responses to cocaine in conscious, unrestrained Sprague-Dawley rats. Surgical adrenal demedullation (ADM) and/or chemical peripheral sympathectomy was used to eliminate one or both components of the sympathoadrenal axis. Phentolamine (5 mg/kg i.v.) was used to evaluate whether cocaine elicited epinephrine (EPI) release from the adrenal medulla. Significant EPI release by cocaine would result in "epinephrine reversal" after phentolamine pretreatment. Cocaine (2.5 mg/kg i.v.) was used in all experiments except the dose-response relationship study. In normal rats, cocaine caused a transient increase in mean blood pressure (MBP). Pretreatment with phentolamine reversed this BP response and this depressor effect was blocked by propranolol (2 mg/kg i.v.) suggesting that the pressor effect of cocaine was mediated by EPI. Chemical sympathectomy alone partially inhibited the pressor effect of cocaine, but pretreatment with phentolamine still reversed the residual action of cocaine on MBP at this time. Two weeks after ADM, the effect of cocaine on MBP was not significantly different from that of the sham-operated rats. However, pretreatment with phentolamine inhibited but did not reverse the effect of cocaine on MBP at that time. In rats with both ADM and chemical sympathectomy, cocaine caused only a decrease in MBP that was not blocked by propranolol or atropine methylnitrate, presumably because of its direct depressive actions. Results of this study suggest that both peripheral sympathetic neurons and the adrenal medulla play important roles in the cardiovascular actions of cocaine.
我们研究了外周交感神经元和肾上腺髓质在清醒、自由活动的Sprague-Dawley大鼠对可卡因的心血管反应中的作用。采用手术切除肾上腺髓质（ADM）和/或化学性外周交感神经切除术来消除交感-肾上腺轴的一个或两个组成部分。使用酚妥拉明（5mg/kg静脉注射）来评估可卡因是否会引起肾上腺髓质释放肾上腺素（EPI）。可卡因引起的显著EPI释放会在酚妥拉明预处理后导致“肾上腺素逆转”。除剂量反应关系研究外，所有实验均使用可卡因（2.5mg/kg静脉注射）。在正常大鼠中，可卡因会导致平均血压（MBP）短暂升高。酚妥拉明预处理可逆转这种血压反应，且这种降压作用可被普萘洛尔（2mg/kg静脉注射）阻断，这表明可卡因的升压作用是由EPI介导的。单独进行化学性交感神经切除术可部分抑制可卡因的升压作用，但此时酚妥拉明预处理仍可逆转可卡因对MBP的残余作用。ADM两周后，可卡因对MBP的作用与假手术大鼠相比无显著差异。然而，此时酚妥拉明预处理可抑制但不能逆转可卡因对MBP的作用。在同时进行ADM和化学性交感神经切除术的大鼠中，可卡因仅导致MBP降低，且不受普萘洛尔或硝酸甲基阿托品的阻断，推测这是由于其直接的抑制作用。本研究结果表明，外周交感神经元和肾上腺髓质在可卡因的心血管作用中均起重要作用。
