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We studied the effects of experimental hemiparkinsonism upon sympathetic function in rat. The rats were divided into three groups: a group given intact control, one given lesioning with 6-hydroxydopamine (6-OHDA), and one given sham operation. One day after apomorphine testing following lesioning of the substantia nigra (SN) with 6-OHDA, heart rate (HR), mean arterial blood pressure (MAP), and electrocardiogram (ECG) were monitored. Plasma norepinephrine (NE), epinephrine (E), and dopamine (DA) levels were measured. Thereafter, immunohistochemical examination was performed to detect the extent of 6-OHDA lesions, using the avidinbiotinylated peroxidase complex (ABC) method. There was no difference in the total number of tyrosine hydroxylase (TH)-positive cells and rotation responses between the right- and left-sided 6-OHDA-treated groups. On the other hand, injury of rats with unilateral 6-OHDA resulted in haemodynamic, electrocardiographic, and biochemical changes. A significant difference was found between the right-sided 6-OHDA-treated rats and the left-sided treated ones. The MAP increased in the group given left 6-OHDA treatment and to lesser extent in the sham-operated group. In contrast, MAP did not increase in the group given right 6-OHDA treatment and was significantly lower than values in both the intact control rats and the sham-treated rats. Also, only the group given right 6-OHDA injury showed a fall in the value of HR. The plasma NE level was significantly decreased in the group given right 6-OHDA treatment compared with all other groups (P < 0.005). Our results indicate that right-sided lesioning of the nigrostriatal DA pathway in the central nervous system (CNS) has greater sympathetic consequences than left-sided ones. These results also suggest that there is a differential effect of right-sided SN lesions on sympathetic cardiac innervation. The mechanism behind the confronting impairment of autonomic nervous system (ANS) could in this experiment be attributable to an asymmetric representation of sympathetic function in the brain. However, further studies will be needed before final conclusions can be made.

1. Isolated superior cervical ganglia of the rat were incubated for 2--30 min (37 degrees C) in Krebs' solution or tissue culture medium (BGJb) containing 22Na and then washed for 30 min in ice-cold 22Na-free Krebs' solution (to clear extracellular space). The radioactivity remaining in the ganglia was taken as a measure of 22Na influx into the intracellular compartment of the ganglion. 2. Addition of cholinomimetics (100 microM nicotine or 100 microM carbachol) to the incubation led to an increase in 22Na influx. This increase reached maximal values after 10 min of incubation; it was more pronounced after incubation in Krebs' solution than in BGJb medium. 3. While chlorisondamine (3 microM) or dopamine (100 microM) greatly reduced the carbachol-induced 22Na influx, tetrodotoxin (2 microM) did not have any effect. 4. In ganglia obtained from animals treated with 6-hydroxydopamine in the early postnatal phase (resulting in an extensive destruction of peripheral sympathetic neurons) neither carbachol (100 microM) nor nicotine (100 microM) produced an increase in 22Na influx demonstrating that the intraneuronal compartment is responsible for this enhanced influx. 5. The effects of dopamine, chlorisondamine and tetrodotoxin on the carbachol-induced 22Na uptake into superior cervical ganglia are similar to their effects on carbachol-mediated induction of tyrosine hydroxylase in superior cervical ganglia kept in tissue culture (Thoenen and Otten 1977b). It is concluded that the induction of tyrosine hydroxylase via nicotinic receptors is closely linked to the enhanced sodium influx into the adrenergic neurons mediated by the same receptors.

The effects of pharmacological alteration of adrenergic transmission on the rate of entrance of dopamine-beta-hydroxylase (DBH) into the circulation were assessed in rats by an immunological method in which the kinetics of recovery of serum DBH activity were measured after depletion of the enzyme by treatment with anti-rat DBH antiserum. Neither alpha-receptor blockade with phenoxybenzamine nor ganglionic blockade with clorisondamine altered the rate by which DBH enters the bloodstream although both treatments markedly altered serum catecholamine levels. Prolonged treatment of newborn rats with guanethidine produced a severe peripheral sympathectomy but only a moderate decrease (30%) in serum DBH levels. In the sympathectomized rats, the rate of entrance of DBH into the circulation was significantly reduced whereas the half-life and rate of degradation of the enzyme was unchanged. These results indicate that the major portion of serum DBH does not enter the circulation by means of exocytotic release of the soluble enzyme.