Sympathetic involvement in vagal escape and the effects of β-receptor blocking drugs

Raper, C.; Wale, Janet

doi:10.1016/0014-2999(69)90128-9

Cited by 12 publications

(4 citation statements)

References 21 publications

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“…A dose was reached which actually potentiated the contractions of the nictitating membrane produced both by nerve stimulation and by injected noradrenaline. These findings explain the failure of Raper & Wale (1968) to demonstrate a presynaptic blocking action of propranolol in the same preparation, since they used both a supramaximal stimulus and large doses of propranolol, 15 mg/kg.…”

Section: Discussionmentioning

confidence: 90%

Factors influencing the adrenergic neurone blocking action of propranolol

Eliash

Weinstock

1972

British J Pharmacology

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Summary1. The reversal by propranolol of its own adrenergic neurone blocking effect in the cat can be prevented by cutting the splanchnic nerves or by ligating the adrenal veins. 2. In the absence of secretion from the adrenal medulla the nerve blocking action of propranolol is more complete, but can still be reversed by repeated injections or a constant infusion of adrenaline.3. Prior treatment with adrenaline or noradrenaline also prevents the development of the blocking action of propranolol in the cat and in the isolated guinea-pig vas deferens. 4. It is suggested that in the cat, propranolol stimulates the release of catecholamines from the adrenal medulla which antagonize its nerve blocking effect. IntroductionIn an earlier publication it was shown that propranolol reduced the effect of

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Section: Discussionmentioning

confidence: 90%

Factors influencing the adrenergic neurone blocking action of propranolol

Eliash

Weinstock

1972

British J Pharmacology

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“…Recently, Eliash & Weinstock (1971) reported that propranolol in low doses reduced contractions of the nictitating membrane of cats by adrenergic neurone-blockade whereas high doses had no effect or caused potentiation. Raper & Wale (1969) also indicated that propranolol in high doses had no inhibitory effect in this preparation. Since responses of non-vascular tissue were employed in these findings, extrapolation to nerves innervating vessels may not be valid.…”

Section: Introductionmentioning

confidence: 85%

The Effect of Propranolol on Vascular Responses to Sympathetic Nerve Stimulation

Dawes¹,

Faulkner²

1975

British J Pharmacology

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In an attempt to clarify the rǒle of the sympathetic neurone in the antihypertensive action of propranolol, the effect of this drug on responses to lumbar sympathetic nerve stimulation has been studied in the perfused hind‐limb of the dog. No consistent reduction of maximal or submaximal responses to nerve stimulation was produced by propranolol (10 to 100 μg/kg). In contrast, potentiation of nerve‐evoked responses, as well as those to injected noradrenaline, usually occurred. Dexpropranolol (50 μg/kg) had no effect. When neuronal uptake of noradrenaline was inhibited by desmethylimipramine or cocaine, no reduction in responses to sympathetic nerve stimulation was observed with propranolol. No evidence was found, using α‐adrenoceptor blocking drugs, that released transmitter stimulates β‐adrenoceptors in the blood vessels of the hind‐limb. No evidence has been found for the existence of an adrenergic neurone‐blocking action of propranolol that might contribute to the antihypertensive activity in man.

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“…Vagal escape usually refers to the two responses of the heart to continuous vagal stimulation: the gradual return of the heart rate toward control level (58,59) and the development of pacemaker activity in multimodal origins (60). Compensation from the sympathetic system has been proposed to cause vagal escape (17)(18)(19)(20). However, since this phenomenon could be observed even in isolated sinoatrial nodes in the presence of a b blocker (52), the cellular machinery associated with the postjunc-tional mechanism was expected to participate in vagal escape.…”

Section: Discussionmentioning

confidence: 99%

“…At the organ level, excess vagal nerve stimulation eventually causes cardiac asystole, followed by resumption of the heartbeat. This desensitization is called vagal escape and has been explained by compensation from the sympathetic system (17)(18)(19)(20). Although ACh causes short-term desensitization of I KACh and vagal escape, the functional relevance of these two different phenomena has not been previously examined.…”

Section: Introductionmentioning

confidence: 99%

Short-Term Desensitization of Muscarinic K+ Current in the Heart

Murakami

Inanobe

Kurachi

2013

Biophysical Journal

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Acetylcholine (ACh) rapidly increases cardiac K(+) currents (IKACh) by activating muscarinic K(+) (KACh) channels followed by a gradual amplitude decrease within seconds. This phenomenon is called short-term desensitization and its precise mechanism and physiological role are still unclear. We constructed a mathematical model for IKACh to examine the conditions required to reconstitute short-term desensitization. Two conditions were crucial: two distinct muscarinic receptors (m2Rs) with different affinities for ACh, which conferred an IKACh response over a wide range of ACh concentrations, and two distinct KACh channels with different affinities for the G-protein βγ subunits, which contributed to reconstitution of the temporal behavior of IKACh. Under these conditions, the model quantitatively reproduced several unique properties of short-term desensitization observed in myocytes: 1), the peak and quasi-steady states with 0.01-100 μM [ACh]; 2), effects of ACh preperfusion; and 3), recovery from short-term desensitization. In the presence of 10 μM ACh, the IKACh model conferred recurring spontaneous firing after asystole of 8.9 s and 10.7 s for the Demir and Kurata sinoatrial node models, respectively. Therefore, two different populations of KACh channels and m2Rs may participate in short-term desensitization of IKACh in native myocytes, and may be responsible for vagal escape at nodal cells.

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Sympathetic involvement in vagal escape and the effects of β-receptor blocking drugs

Cited by 12 publications

References 21 publications

Factors influencing the adrenergic neurone blocking action of propranolol

Factors influencing the adrenergic neurone blocking action of propranolol

The Effect of Propranolol on Vascular Responses to Sympathetic Nerve Stimulation

Short-Term Desensitization of Muscarinic K+ Current in the Heart

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