Lokhandwala M F, Buckley J P, Jandhyala B S
Eur J Pharmacol. 1976 May;37(1):79-89. doi: 10.1016/0014-2999(76)90010-8.
Oral administration of methyldopa (100 mg/kg, twice daily for 3 days) to mongrel dogs produced a significant decrease in blood pressure and heart rate. The drug treatment affected neither the resting venous tone nor the cardiac output. Thus, the hypotensive effect of the drug was predominantly due to a reduction in total peripheral resistance. Vasoconstrictor responses of the renal vasculature to sympathetic nerve stimulation were significantly impaired after methyldopa at all the frequencies, while mesenteric vasoconstrictor responses to sympathetic nerve stimulation were impaired only at the lower stimulation frequencies. In addition, methylnorepinephrine was a significantly less potent vasoconstrictor than norepinephrine in the renal vasculature, but was equipotent to norepinephrine in the mesentery. The finding of a reduction in the renal vascular resistance of methyldopa-treated dogs, with no such alteration in the mesenteric vascular resistance, is consistent with the nerve stimulation studies. Therefore, the results of the present investigation indicate that in addition to the existing evidence favoring a central site of action for methyldopa, the impairment of peripheral sympathetic neuronal function is also of importance in accounting for the hemodynamic alterations observed following treatment with methyldopa.
给杂种犬口服甲基多巴（100毫克/千克，每日两次，共3天）可使血压和心率显著降低。药物治疗对静息静脉张力和心输出量均无影响。因此，该药物的降压作用主要是由于总外周阻力降低。甲基多巴处理后，在所有频率下，肾血管对交感神经刺激的血管收缩反应均显著受损，而肠系膜血管对交感神经刺激的血管收缩反应仅在较低刺激频率下受损。此外，在肾血管中，甲基去甲肾上腺素作为血管收缩剂的效力明显低于去甲肾上腺素，但在肠系膜中与去甲肾上腺素效力相当。甲基多巴处理的犬肾血管阻力降低，而肠系膜血管阻力无此改变，这一发现与神经刺激研究结果一致。因此，本研究结果表明，除了现有证据支持甲基多巴的作用部位在中枢外，外周交感神经神经元功能受损在解释甲基多巴治疗后观察到的血流动力学改变方面也很重要。
