Harland D, Brown M J
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London, United Kingdom.
J Pharmacol Exp Ther. 1988 Apr;245(1):265-73.
To test the hypothesis that alpha-2 adrenoceptor antagonists can modulate sympathetic nerve release of norepinephrine in vivo through blockade of peripheral prejunctional alpha-2 adrenoceptors, acute and chronic effects of the alpha-2 adrenoceptor antagonist idazoxan on mean arterial pressure (MAP), heart rate and plasma catecholamine concentrations have been investigated in conscious and anesthetized rats. In normotensive rats, a single i.v. dose of idazoxan (300 micrograms kg-1) caused an immediate 2-fold increase in plasma concentration of norepinephrine and epinephrine, a transient increase in heart rate but no significant change in MAP. Plasma norepinephrine concentration of conscious normotensive rats increased significantly during a 4-hr i.v. infusion of idazoxan (300 micrograms kg-1 hr-1) with no concomitant changes in MAP or heart rate. In anesthetized spontaneously hypertensive rats, the increases in plasma norepinephrine concentration and heart rate caused by i.v. idazoxan (300 micrograms kg-1) were accompanied by a significant decrease in MAP. The increase in plasma norepinephrine after idazoxan in spontaneously hypertensive rats was much greater than that produced by an equihypotensive dose of the vasodilator hydralazine. Normotensive rats treated continuously for 7 days with s.c. idazoxan (7.5 mg kg-1 day-1) had similar blood pressures and plasma catecholamine concentrations to vehicle-treated rats. These results suggest that idazoxan causes a greater increase in plasma norepinephrine concentration than that which can be attributed to baroreceptor stimulation. Blockade of prejunctional alpha-2 adrenoceptors by idazoxan may, therefore, increase release of norepinephrine from peripheral sympathetic nerves of anesthetized and conscious rats. This effect is short-lived and does not influence blood pressure of normotensive rats.
为了验证α-2肾上腺素能受体拮抗剂可通过阻断外周突触前α-2肾上腺素能受体来调节体内交感神经去甲肾上腺素释放这一假说，研究了α-2肾上腺素能受体拮抗剂咪唑克生对清醒和麻醉大鼠平均动脉压（MAP）、心率及血浆儿茶酚胺浓度的急性和慢性影响。在正常血压大鼠中，静脉注射单次剂量的咪唑克生（300微克/千克）可使去甲肾上腺素和肾上腺素的血浆浓度立即增加2倍，使心率短暂增加，但MAP无显著变化。清醒正常血压大鼠在静脉输注咪唑克生（300微克/千克·小时）4小时期间，血浆去甲肾上腺素浓度显著增加，而MAP和心率无相应变化。在麻醉的自发性高血压大鼠中，静脉注射咪唑克生（300微克/千克）引起的血浆去甲肾上腺素浓度和心率增加伴随着MAP的显著降低。自发性高血压大鼠注射咪唑克生后血浆去甲肾上腺素的增加幅度远大于等降压剂量的血管扩张剂肼屈嗪所产生的增加幅度。用皮下注射咪唑克生（7.5毫克/千克·天）连续处理7天的正常血压大鼠，其血压和血浆儿茶酚胺浓度与用赋形剂处理的大鼠相似。这些结果表明，咪唑克生引起的血浆去甲肾上腺素浓度增加幅度大于可归因于压力感受器刺激的增加幅度。因此，咪唑克生对突触前α-2肾上腺素能受体的阻断可能会增加麻醉和清醒大鼠外周交感神经去甲肾上腺素的释放。这种作用是短暂的，且不影响正常血压大鼠的血压。
