Lokhandwala M F, Buckley J P, Jandhyala B S
Eur J Pharmacol. 1975 Jun-Jul;32(02):170-8. doi: 10.1016/0014-2999(75)90280-0.
Administration of methyldopa (100 mg/kg, p.o. twice daily for 3 days) to mongrel dogs produced a significant decrease in the mean blood pressure (MBP) and heart rate (HR). Chronotropic responses to cardioaccelerator nerve stimulation and vasoconstrictor responses to lumbar sympathetic nerve stimulation were significantly attenuated in the treated dogs. Pressor and chronotropic responses to bilateral carotid occlusion (BCO) and tyramine were also markedly reduced following treatment with methyldopa, which is consistent with the clinical findings that chronic methyldopa treatment in hypertensive patients impairs cardiovascular reflexes. Methylnorepinephrine (MNE) was significantly less potent than norepinephrine (NE) in producing an increase in MBP or hindleg perfusion pressure, while the chronotropic and inotropic potency of MNE was about equal to NE. These results indicate that treatment with methyldopa in the dog does indeed produce an impairment of peripheral sympathetic neuronal function to certain organs and this peripheral effect of the drug may be of importance in accounting for its antihypertensive action in the dog.
给杂种犬口服甲基多巴（100毫克/千克，每日两次，共3天）后，平均血压（MBP）和心率（HR）显著降低。在接受治疗的犬中，对心脏加速神经刺激的变时反应以及对腰交感神经刺激的血管收缩反应均显著减弱。在用甲基多巴治疗后，对双侧颈动脉闭塞（BCO）和酪胺的升压和变时反应也明显降低，这与高血压患者长期接受甲基多巴治疗会损害心血管反射的临床发现一致。在升高MBP或后肢灌注压方面，甲基去甲肾上腺素（MNE）的效力明显低于去甲肾上腺素（NE），而MNE的变时和变力效力与NE大致相当。这些结果表明，犬使用甲基多巴治疗确实会导致外周交感神经元对某些器官的功能受损，并且该药物的这种外周效应可能在解释其对犬的降压作用中具有重要意义。
