Role of norepinephrine in the rabbit ganglionectomy response.

Superior cervical ganglionectomy (SCG) produced delayed mydriasis and ocular hypotension in rabbits. Norepinephrine (NE) was lost from the iris-ciliary body exponentially with onset of about 11 h. NE in aqueous humor peaked at twice control levels (from 7 to 14 ng/ml) at 16.5 h and subsequently declined to below control levels by 24 h. Intracameral administration of radiolabeled NE (150 ng) to control eyes resulted in a calculated outflow of 1.6 microliter/min, comparable to that seen with fluorescein (1.7 microliter/min). NE administered to ganglionectomized eyes (26 h after surgery) resulted in a calculated outflow of 3.1 microliter/min. These results suggest that mydriasis following SCG may be due to NE released from degenerating sympathetic nerve endings. However, NE concentration in the aqueous humor appears inadequate to produce the delayed increase in outflow observed in rabbits after SCG.

Evidence for two distinct sympathoinhibitory bulbo-spinal systems.

Yohimbine hydrochloride (0.5 mg/kg, i.v.) caused a long-lasting potentiation of electrodermal (sympathetic-cholinergic) reflexes in intact anaesthetized and decerebrate unanaesthetized cats. Transection of the cervical spinal cord also resulted in an increased amplitude of the sudomotor reflex in unanaesthetized decerebrate preparations. Depletion of monoamines in the CNS by pretreatment with reserpine (5 mg/kg, i.p.) and alpha-methyl-p-tyrosine (2 X 300 mg/kg, i.p.) reduced the concentrations of norepinephrine, dopamine and serotonin to less than 93% of control levels in the thoracic spinal cord. In monoamine-depleted preparations, yohimbine no longer facilitated the reflex amplitude whereas the effect of spinal transection was not altered. These results suggest that there are two distinct sympathoinhibitory systems in the lower brain stem that converge on spinal sympathetic neurons, one of which is monoaminergic and one of which is not. Evidence for the baroreceptor-independent nature of these descending inhibitory systems is discussed.

Use of a sympathetic-cholinergic system in the analysis of sympatho-inhibition produced by clonidine and some congeneric derivatives of clonidine.

The effects of clonidine and five analogs of clonidine were tested with regard to their ability to depress centrally and peripherally evoked electrodermal responses (EDR) in control cats, as well as in animals pretreated with yohimbine hydrochloride. With the exception of St-91, all of the clonidine-like substances selectively reduced the amplitude of centrally (hypothalamic) evoked responses in a dose-dependent fashion. Clonidine was found to have no significant inhibitory effect at the level of the sympathetic ganglion. The order of central nervous system sympatho-inhibitory potency of these compounds was clonidine (St-155) greater than St-375 greater than St-606 greater than St-600 greater than St-608 much much greater than St-91. Prior treatment with yohimbine hydrochloride (0.5 mg/kg i.v.) antagonized the depressant effect of all of these drugs. These results indicate that clonidine and the clonidine congeners tested (with the exception of St-91) all produce sympatho-inhibition by an action on a CNS alpha-adrenergic mechanism and demonstrate the usefulness of this electrodermal model system for the analysis of drugs affecting central sympathetic reactivity.

Effects of clonidine and chlorpromazine on a sympathetic-cholinergic reflex.

Intravenous administration of clonidine and chlorpromazine resulted in a dose-dependent inhibition of the amplitude of reflexly evoked electrodermal responses in intact and spinal cats. Yohimbine pretreatment (0.5 mg/kg, i.v.) antagonized the effects of clonidine but not chlorpromazine in both preparations. These findings confirm and expand previous observations that both clonidine and chlorpromazine inhibit the amplitude of centrally evoked responses in this sympathetic-cholinergic system. In addition, both drugs appeared to have a spinal site of action. The antagonism of the effects of clonidine by yohimbine suggests that the mechanism of the action of clonidine may be a result of activation of central inhibitory alpha-adrenergic receptors. The failure of yohimbine to antagonize the effects of chlorpromazine suggests that clonidine and chlorpromazine may depress these sympathetic reflexes by different mechanisms.

Some physiologic characteristics of the electrodermal reflex in the cat.

The amplitudes of electrodermal reflexes evoked in intact cats were compared under a variety of anesthetic conditions. Electrodermal reflexes were elicited in both decerebrate and spinal preparations with and without anesthesia. Reflex amplitude was significantly depressed in the anesthetized preparation after decerebration or spinal transection. In contrast, spinal transection performed after decerebration in unanesthetized preparations significantly increased the amplitude of the reflex. The evidence presented in this study supports the concept of a primarily inhibitory lower brainstem system with regard to this reflex. The relative stability of the reflex amplitude in the anesthetized cat suggests that this reflex system could be useful in the analysis of the effects of drugs acting on the central nervous system.

Epinephrine inhibition of the electrodermal response in the cat.

Intravenous administration of epinephrine results in a dose-dependent inhibition of the peripherally evoked electrodermal response (EDR) in the cat. The magnitude of this depression of the EDR was greater when the responses were evoked by a single shock than by a train of shocks (10-12 Hz). The observation that this epinephrine-induced inhibition is antagonized by phentolamine suggests that an alpha-adrenergic mechanism is involved. It is unlikely that this effect is due primarily to the vascular actions of epinephrine because the inhibition of the EDR was much more prolonged than was the pressor action. Angiotensin was ineffective in inhibiting these responses.