Studies on the mechanism of the cardiovascular effects of methyldopa



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Administration of methyldopa to mongrel dogs (100mg/kg., p.o. twice daily for three days) produced a significant decrease in blood pressure, heart rate and coronary, renal as well as total peripheral resistance. Cardiac output was unaltered and the drug treatment did not produce any change in venous compliance or in left ventricular function. Responses to sympathetic nerve stimulation in various cardiovascular organs were significantly impaired following treatment with methyl dopa. Certain cardiovascular reflexes were also significantly attenuated in methyl dopa treated dogs. Methyl norepinephrine was either equipotent to or less potent than norepinephrine depending on the organs studied. These results indicate that antihypertensive action of methyldopa in mongrel dogs is mediated by a decrease in the peripheral resistance and in addition to the existing evidence favoring a central site of action for methyldopa, the present investigation has demonstrated that impairment of peripheral sympathetic neuronal function plays an important role in producing the cardiovascular effects observed following the drug treatment.