Minami K, Yanagihara N, Segawa K, Tsutsui M, Shigematsu A, Izumi F
Department of Anaesthesiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 1996 Apr;353(5):572-8. doi: 10.1007/BF00169178.
In the central and peripheral noradrenergic neurons, the balance between noradrenaline release and reuptake determines the level of noradrenaline at the synaptic cleft or the nerve ending. In the present study, we examined the effects of propofol, an intravenous general anaesthetic, on catecholamine secretion and noradrenaline uptake in cultured bovine adrenal medullary cells and on the serum noradrenaline and blood pressure in rats. In cultured adrenal medullary cells, propofol (10-50 mumol/l) concentration-dependently inhibited catecholamine secretion stimulated by carbachol. Propofol suppressed carbachol-evoked 22Na+ influx as well as 45Ca2+ influx at concentrations similar to those which suppressed the catecholamine secretion. Propofol (10-50 mumol/l) also inhibited veratridine-evoked 22Na+ influx, 45Ca2+ influx and catecholamine secretion, whereas it had little effect on the 45Ca2+ influx and catecholamine secretion induced by 56 mmol/l K+. Cultured adrenal medullary cells show [3H] noradrenaline uptake which is sensitive to imipramine. Propofol (10-50 mumol/l) significantly inhibited the imipramine-sensitive uptake of [3H] noradrenaline. In rats, intravenous administration of propofol (2.5 mg/kg) lowered serum noradrenaline and arterial blood pressure. From these findings, in spite of inhibiting noradrenaline uptake, propofol at anaesthetic concentrations (10-30 mumol/l) seems to reduce catecholamine secretion by interfering with Na+ influx through voltage-dependent Na+ channels as well as nicotinic acetylcholine receptor-associated ion channels in the adrenal medulla and, probably, in the sympathetic nervous system. This may explain the propofol-induced hypotension during anaesthesia.
在中枢和外周去甲肾上腺素能神经元中，去甲肾上腺素释放与再摄取之间的平衡决定了突触间隙或神经末梢处去甲肾上腺素的水平。在本研究中，我们检测了静脉全身麻醉药丙泊酚对培养的牛肾上腺髓质细胞中儿茶酚胺分泌和去甲肾上腺素摄取的影响，以及对大鼠血清去甲肾上腺素和血压的影响。在培养的肾上腺髓质细胞中，丙泊酚（10 - 50 μmol/L）呈浓度依赖性地抑制卡巴胆碱刺激的儿茶酚胺分泌。丙泊酚在抑制儿茶酚胺分泌的浓度下，也抑制了卡巴胆碱诱发的22Na+内流以及45Ca2+内流。丙泊酚（10 - 50 μmol/L）还抑制了藜芦碱诱发的22Na+内流、45Ca2+内流和儿茶酚胺分泌，而对56 mmol/L K+诱导的45Ca2+内流和儿茶酚胺分泌影响很小。培养的肾上腺髓质细胞表现出对丙咪嗪敏感的[3H]去甲肾上腺素摄取。丙泊酚（10 - 50 μmol/L）显著抑制了对丙咪嗪敏感的[3H]去甲肾上腺素摄取。在大鼠中，静脉注射丙泊酚（2.5 mg/kg）可降低血清去甲肾上腺素和动脉血压。从这些发现来看，尽管丙泊酚抑制去甲肾上腺素摄取，但麻醉浓度（10 - 30 μmol/L）的丙泊酚似乎通过干扰肾上腺髓质以及可能交感神经系统中电压依赖性Na+通道和烟碱型乙酰胆碱受体相关离子通道的Na+内流来减少儿茶酚胺分泌。这可能解释了麻醉期间丙泊酚诱导的低血压。
