THE EFFECT OF l-DOPA ON CHRONOTROPIC RESPONSES TO CARDIOACCELERATOR NERVE STIMULATION IN DOGS

¹ Departments of Pharmacology and Medicine (Division of Clinical Pharmacology), University of Cincinnati College of Medicine, Cincinnati, Ohio

Postural hypotension is often seen during treatment with l-dopa in patients with parkinsonism. In view of the possibility that this effect might be related to sympathetic impairment, the chronotropic responses to pre- and postganglionic cardioaccelerator nerve stimulation (1-30 cps) and to i.v. norepinephrine (0.3-10 µg/kg) were compared before and three to six hours after a single i.v. injection of l-dopa (100 mg/kg). Injection of l-dopa led to an increase in heart rate lasting for an average of four hours, and to an initial rise followed by a fall in systemic arterial pressure. Chronotropic responses to both cardioaccelerator nerve stimulation and norepinephrine were significantly reduced after l-dopa. Because administration of l-dopa produced acidosis, sodium bicarbonate was given i.v. to maintain blood pH within physiologic range; this did not affect the magnitude of impairment in chronotropic responses to cardioaccelerator nerve stimulation produced by l-dopa but the degree of impairment in chronotropic responses to norepinephrine was significantly reduced. Systemic pressor responses to norepinephrine decreased after l-dopa only in those experiments in which acidosis was present. These data suggest that l-dopa interferes with postganglionic nerve function.