The Effect of Denervation on the Action of Sympathomimetic Amines on the Nictitating Membrane

Abstract

The work of Cannon and Rosenblueth and their collaborators on the hypersensitivity of denervated structures has given rise to a general impression that after the denervation of a tissue there is always an increased response to a chemical stimulus. However, there are notable exceptions to this rule even among the limited class of sympathomimetic amines acting on structures innervated by postganglionic sympathetic fibres. Burn and Tainter (1931) observed that the iris of the cat's eye was insensitive to the dilator action of tyramine and much less sensitive to that of ephedrine when the superior cervical ganglion was removed one or two weeks previously. On the iris of the rabbit Drake, John, Renshaw, and Thienes (1939) found that p-hydroxyamphetamine, which caused dilatation of the normal iris, failed to do so after denervation. Burn (1932) found that the constrictor action of tyramine and of ephedrine in the vessels of the cat's foreleg was diminished or abolished by removal of the stellate ganglion 2-3 weeks previously. These results suggested that the effect of tyramine was depressed by denervation in all tissues, but Bacq (1937) stated that this conclusion did not hold good for the nictitating membrane in the cat under Dial anaesthesia. Bu1bring and Burn (1938) therefore investigated the action of tyramine in a series of cats and found that the most usual result was that the denervated membrane was more sensitive to low doses, but the normal membrane was more sensitive to high doses.At the same time they investigated hydroxytyramine and neosynephrine (Sympatol). Their general conclusion was that the more the structure of the compound departed from that of adrenaline the more often the denervated membrane was found to respond less than the normal membrane.While it was thus clear that substances such as tyramine and ephedrine did not stimulate denervated tissue in general as much as normal tissue, the change in the response of the nictitating membrane in the early period after the operation was still unknown. We have therefore studied this question in some detail with a wider range of substances, and have been able to show that sympathomimetic amines fall into three groups so far as their action on the denervated membrane is concerned. METHOD The right superior cervical ganglion was removed in an aseptic operation on each of 60 cats. After a varying interval each cat was anaesthetized with ether, and the spinal cord was divided by Dale's method (Burn, Finney, and Goodwin, 1950) without clamping the carotid arteries during the operation. The anaesthetic was discontinued and artificial respiration was given. The left cervical sympathetic chain was cut. The cat's head was then fixed rigidly and threads were passed through the nictitating membranes so that their contractions could be recorded by an isotonic lever which magnified the contractions 7.4 times. The blood pressure was recorded from one femoral artery and injections were made into the femoral vein of the opposite side. RESULTSThe sympathomimetic amines w...

The Effects of Reserpine on the Responses of the Nictitating Membrane in the Cat

“…These results ob`ained in this experiments concerning the increased responses of the denervated membrane to the sympathomimetic amines well agreed with the results showed by Trendelenburg (18). It was reported that the response of the nicti:ating membrane to tyramine was decreased by the denervation (19). The difference between their results and the present results may be supposed to consist in the dose of tyramine, because the dose of tyramine in this experiment was one-tenth of their dosage.…”

Mechanism of Cardiovascular Actions of Heptanolamines

“…Heptanolamines are not a substrate of mono-amine oxidase nor do they inhibit this enzyme, and this fact makes it possible to exclude enzymatic inhibition as part of the effects of these substances. It is known (Fleckenstein & Bass, 1953;Fleckenstein & Burn, 1953;Fleckenstein & Stockle, 1955) that the actions of some aromatic amines like tyramine are antagonized by cocaine and denervation. Later work (Carlsson, Rosengren, Bertler & Nilsson, 1957; Burn & Rand, 1958;Holtz, Osswald & Stock, 1960) showed that treatment with reserpine induces modifications in the activity of these amines which duplicate those occurring after cocaine or denervation.…”

Pressor responses to ephedrine are not impaired in dopamine β‐hydroxylase knockout mice

“…However, the mechanism of the pressor response to ephedrine is uncertain. Ephedrine has been thought to elicit a pressor response through the release of noradrenaline from adrenergic terminals (Fleckenstein and Burn, 1953;Burn and Rand, 1958;DeMoraes and Carvalho, 1968;Kobayashi et al, 2003). It has been reported that the pressor response to ephedrine is reduced following treatment with 6-hydroxydopamine to destroy adrenergic nerve terminals (Kobayashi et al, 2003).…”