RELAXATION OF SMOOTH MUSCLE FOLLOWING CONTRACTION ELICITED BY SYMPATHETIC NERVE STIMULATION in vivo

Abstract

A method for studying in vivo the process of neuroeffector transmission in the nictitating membrane and nasal blood vessels of the cat is described. 2 Administration of desmethylimipramine or cocaine caused increases in both the amplitude and duration of the nasal and membrane responses which may be explained by inhibition of neuronal uptake of noradrenaline. 3 Phenoxybenzamine depressed the responses to nerve stimulation, but had little effect on the relationship between response amplitude and rate of recovery. 4 The relationship between response amplitude and rate of recovery is discussed and related to the sigmoid shape of a log concentration-response curve.

THE INFLUENCE OF AN EXTRANEURONAL COMPARTMENT ON THE RELAXATION OF THE CAT NICTITATING MEMBRANE in vivo

“…In three experiments desipramine (0.2 mg/kg i.v.) slowed the initial phase of the relaxation, a result which we have already reported (Eccles & MacLean, 1977). Under these conditions the transition between the early and late phases of relaxation was more abrupt and occurred at an amplitude which increased with the period of stimulation.…”

“…Desipramine dose-dependently reduces the initial rate of relaxation of nictitating membrane responses (Eccles & MacLean, 1977), presumably through its inhibitory action on the neuronal uptake process (Titus & Spiegel, 1962). This inhibition may explain why the relaxation of the nictitating membrane after high frequency stimulation occurs in three distinct phases following the administration of desipramine 1.2 mg/kg: 1) during the initial phase the extracellular concentration of noradrenaline drops rapidly until it reaches a level where the removal of noradrenaline by neuronal uptake is exactly balanced by a net efflux from extraneuronal stores; 2) during the middle or 'holding' phase this efflux from the extraneuronal stores continues until the concentration of noradrenaline in these stores is so reduced that the rate of efflux no longer compensates for the activity of the neuronal uptake process; 3) the late phase of relaxation represents the period during which the extracellular concentration of noradrenaline is once more declining although more slowly than during the initial phase as there is still some slow efflux from the extraneuronal stores.…”

“…In vivo the relaxation of the cat nictitating membrane, after a period of nerve stimulation, has been reported to occur in two or three phases following inhibition of the neuronal uptake process; this pattern of relaxation was attributed to the mechanism described above (Eccles & MacLean, 1977).…”

Methoxyphenamine inhibits basal and histamine‐induced nasal congestion in anaesthetized rats

“…Adrenaline or noradrenaline either administered into the circulation or applied directly to the nasal mucosa cause pronounced nasal vasoconstriction (Malcomson, 1959;Jackson, 1970). These vasoconstrictor responses are mediated by a-adrenoceptors and are reduced after administration of a-adrenoceptor antagonists such as phentolamine (Eccles & MacLean, 1977). Drugs such as cocaine and desmethylimipramine which interfere with the neuronal uptake of noradrenaline into nerve endings therefore potentiate the nasal vasoconstriction induced by sympathetic nerve stimulation (Eccles & MacLean, 1977) but reduce the effects of indirectly acting sympathomimetic amines.…”

“…These vasoconstrictor responses are mediated by a-adrenoceptors and are reduced after administration of a-adrenoceptor antagonists such as phentolamine (Eccles & MacLean, 1977). Drugs such as cocaine and desmethylimipramine which interfere with the neuronal uptake of noradrenaline into nerve endings therefore potentiate the nasal vasoconstriction induced by sympathetic nerve stimulation (Eccles & MacLean, 1977) but reduce the effects of indirectly acting sympathomimetic amines. In summary, the present study provides evidence that methoxyphenamine has nasal decongestant properties in the rat.…”