Mahlakaarto J, Ruskoaho H, Huttunen P, MacDonald E, Pasanen M
Department of Pharmacology and Toxicology, Biocenter Oulu, University of Oulu, Finland.
Toxicology. 1998 Jul 3;128(2):101-11. doi: 10.1016/s0300-483x(98)00053-5.
We examined the effects of intravenously administered cocaine and norcocaine on the haemodynamics, the plasma immunoreactive atrial natriuretic peptide (ANP), the N-terminal peptide of proANP (NT-ANP) and the plasma catecholamine levels in conscious, chronically cannulated Sprague-Dawley rats. Cocaine caused an immediate significant peak rise in the mean arterial pressure which was followed by a dose-dependent sustained pressor response. Cocaine also decreased the heart rate and increased the right atrial pressure. Norcocaine at a dose of 1 mg/kg maximally decreased the heart rate which did not recover to the basal level within 15 min. Norcocaine (1 mg/kg) did not affect the right atrial pressure but with a dose of 3 mg/kg an elevation of 2.2 +/- 0.3 mmHg (P < 0.005) was observed which did not recover to the control level during the 30 min study period. Plasma immunoreactive ANP and NT-ANP levels increased significantly in a dose-dependent manner after the injection of cocaine. Norcocaine treatments also resulted in significant correlations between ANP or NT-ANP levels and haemodynamic variables, especially between the right atrial pressure and the plasma immunoreactive ANP levels (r = 0.58, n = 28, P < 0.005). Cocaine and norcocaine enhanced the plasma adrenaline levels but norcocaine, already at a dose of 1 mg/kg, caused a maximal increase in the plasma adrenaline levels. The long lasting increase in the right atrial pressure after norcocaine and the decrease in the heart rate after higher doses of cocaine suggest the role for this metabolite, or a further metabolite of norcocaine, in the cardiovascular and haemodynamic responses to cocaine seen in conscious rats.
我们研究了静脉注射可卡因和去甲可卡因对清醒、长期插管的Sprague-Dawley大鼠的血流动力学、血浆免疫反应性心房利钠肽（ANP）、前ANP的N端肽（NT-ANP）以及血浆儿茶酚胺水平的影响。可卡因使平均动脉压立即出现显著的峰值升高，随后是剂量依赖性的持续升压反应。可卡因还降低了心率并升高了右心房压力。剂量为1mg/kg的去甲可卡因最大程度地降低了心率，且在15分钟内未恢复到基础水平。去甲可卡因（1mg/kg）不影响右心房压力，但剂量为3mg/kg时，观察到右心房压力升高2.2±0.3mmHg（P<0.005），在30分钟的研究期间未恢复到对照水平。注射可卡因后，血浆免疫反应性ANP和NT-ANP水平呈剂量依赖性显著升高。去甲可卡因处理也导致ANP或NT-ANP水平与血流动力学变量之间存在显著相关性，尤其是右心房压力与血浆免疫反应性ANP水平之间（r = 0.58，n = 28，P<0.005）。可卡因和去甲可卡因提高了血浆肾上腺素水平，但去甲可卡因在剂量为1mg/kg时就使血浆肾上腺素水平出现最大程度升高。去甲可卡因后右心房压力的持久升高以及高剂量可卡因后心率的降低表明该代谢产物或去甲可卡因的进一步代谢产物在清醒大鼠对可卡因的心血管和血流动力学反应中发挥作用。
