Feria M, Alvarez C, Domínguez J, Sánchez A, Boada J
Department of Pharmacology, Faculty of Medicine, University of La Laguna, Tenerife, Spain.
J Pharmacol Exp Ther. 1990 Nov;255(2):523-8.
The work was aimed at analyzing the ability of naloxone to potentiate 1) the arterial pressure responses to sympathomimetic amines administered i.v. in normotensive anesthetized, pithed, chemically sympathectomized or acutely adrenalectomized rats and 2) the chronotropic responses to norepinephrine in the isolated rat atria. In anesthetized rats, naloxone (2.5-10 mg/kg i.v.) potentiated the pressor responses to epinephrine (2 micrograms/kg). Naloxone (5 mg/kg) significantly potentiated the pressor responses to norepinephrine (1-4 micrograms/kg), phenylephrine (10-50 micrograms/kg) and the reflex pressor responses to a 60-sec carotid occlusion. On the contrary, naloxone did not potentiate the arterial pressure responses to methoxamine (100 micrograms/kg), angiotensin (0.5-2 micrograms/kg) and isoproterenol (1 micrograms/kg). Pithing or acute adrenalectomy did not alter the naloxone-induced potentiation of the pressor responses to norepinephrine (0.125-0.5 micrograms/kg). 6-Hydroxydopamine pretreatment abolished completely the naloxone-induced potentiation of the pressor responses to norepinephrine (0.25-1 micrograms/kg). In isolated rat atria, naloxone (1.4 and 2.8 x 10(-5) M) potentiated the chronotropic responses to norepinephrine (1.5-6 x 10(-8) M). It is suggested that naloxone potentiates cardiovascular responses to sympathomimetic amines by interacting with presynaptic adrenergic mechanisms which could additionally contribute to its pressor effects in acute hypotensive conditions.
1)在正常血压的麻醉大鼠、去脑大鼠、化学性交感神经切除大鼠或急性肾上腺切除大鼠中,静脉注射拟交感胺后引起的动脉血压反应;2)在离体大鼠心房中,去甲肾上腺素引起的变时反应。在麻醉大鼠中,纳洛酮(静脉注射2.5 - 10mg/kg)增强了对肾上腺素(2μg/kg)的升压反应。纳洛酮(5mg/kg)显著增强了对去甲肾上腺素(1 - 4μg/kg)、去氧肾上腺素(10 - 50μg/kg)的升压反应以及对60秒颈动脉阻断的反射性升压反应。相反,纳洛酮并未增强对甲氧明(100μg/kg)、血管紧张素(0.5 - 2μg/kg)和异丙肾上腺素(1μg/kg)的动脉血压反应。去脑或急性肾上腺切除并未改变纳洛酮诱导的对去甲肾上腺素(0.125 - 0.5μg/kg)升压反应的增强作用。6 - 羟基多巴胺预处理完全消除了纳洛酮诱导的对去甲肾上腺素(0.25 - 1μg/kg)升压反应的增强作用。在离体大鼠心房中,纳洛酮(1.4和2.8×10⁻⁵M)增强了对去甲肾上腺素(1.5 - 6×10⁻⁸M)的变时反应。提示纳洛酮通过与突触前肾上腺素能机制相互作用来增强对拟交感胺的心血管反应,这可能额外有助于其在急性低血压状态下的升压作用。