Studies on the mechanism of the cardiovascualr effects of methyldopa.

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.