In anesthetized dogs and cats, intravenous L-dopa reduced the increase in mean blood pressure in response to bilateral carotid occlusion by 77.5% (P<0.01). In the presence of a dopa decarboxylase inhibitor (Ro 4-4602), this effect was absent. Transmission across the superior cervical sympathetic ganglion in the cat was unaltered by the administration of L-dopa. Carotid artery infusion in the dog of 20% of the effective intravenous dose of L-dopa or dopamine failed to inhibit the response to bilateral carotid occlusion. The pressor response to intravenous tyramine in the dog was potentiated (P<0.05) by L-dopa. In the dog, the increase in femoral vascular resistance to lumbar sympathetic nerve stimulation was attenuated (P < 0.05) by L-dopa while the response to intra-arterial norepinephrine was unchanged. Thus, inhibition of postganglionic sympathetic nerve activity is a possible mechanism by which L-dopa impaired the carotid sinus reflex.
ADDITIONAL KEY WORDScat dog carotid sinus reflex decarboxylase inhibition ganglionic transmission dopamine norepinephrine tyramine• Patients with Parkinson's disease treated with L-dopa have frequently experienced orthostatic hypotension (1-6). Although a number of theories have been proposed to explain this phenomenon, the mechanism of action has not yet been elucidated. In the present study we found that the pressor response to bilateral carotid artery occlusion of anesthetized dogs and cats was markedly impaired by intravenous administration of Ldopa. By systematic elimination of several possible mechanisms, we conclude that impairment of the activity of postganglionic sympathetic nerves is the most likely explana- emulation Research. Vol. XXVU, October 1970 tion for the attenuation of the carotid sinus reflex.
Methods
STUDIES IN THE DOGMongrel dogs (11 to 17 kg) were anesthetized with pentobarbital (25 mg/kg iv). This was followed by a continuous infusion of the drug at a rate of approximately 5 mg • kg" 1 • hour-1 . Ventilation was provided by a Harvard respirator pump. Esophageal temperature was maintained at 37°C by electric heating pads applied to the surface of the body. After bilateral vagotomy, the common carotid arteries were isolated several centimeters proximal to the carotid sinus and loose cotton ligatures were placed around them. To occlude the arteries, the ligatures were pulled gently through a piece of polyethylene tubing for 30 seconds. The response to two or more carotid occlusion tests was obtained before, during, and after L-dopa administration.Blood pressure was measured from a femoral artery by a Statham P23-D transducer and electrically integrated mean blood pressure was recorded on a Grass polygraph. A femoral vein was used for intravenous injections and infusions. An initial loading dose (5 mg/kg) of L-dopa was administered, followed by a continuous infusion ( 0.2 mg • kg-1 • min-1 ). In four animals the infusion rate was increased 25 to 90% to attenuate 561 by guest on May 7, 2018
