α1-Adrenoceptor activation can increase heart rate directly or decrease it indirectly through parasympathetic activation

Nicholas Flavahan, J. C. McGrath

Research output: Contribution to journalArticle

Abstract

The chronotropic effects of α- and β-adrenoceptor agonists were investigated in the pithed rat. The β-adrenoceptor agonist, isoprenaline, produced only a positive chronotropic response. α1-Adrenoceptor agonists, phenylephrine and amidephrine, produced positive and negative chronotropic effects. Part of the response to phenylephrine was β-mediated. A positive chronotropic response to amidephrine and phenylephrine was mediated directly through cardiac α1-adrenoceptors and had a different time course from β-adrenoceptor-mediated responses. A negative chronotropic response to α-agonists was potentiated by neostigmine and blocked by atropine, tetrodotoxin or hexamethonium as well as by α1-adrenoceptor antagonists. This may indicate α1-adrenoceptors on preganglionic parasympathetic nerves, stimulation of these receptors causing release of acetylcholine. The α2-adrenoceptor agonist, xylazine, produced a direct negative chronotropic effect on the heart, independent of α-adrenoceptors. No evidence was found for functional post-junctional α2-adrenoceptors. At high doses xylazine stimulated cardiac α1-adrenoceptors.

Original languageEnglish (US)
Pages (from-to)319-328
Number of pages10
JournalBritish Journal of Pharmacology
Volume77
Issue number2
StatePublished - 1982
Externally publishedYes

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Adrenergic Receptors
Heart Rate
Phenylephrine
Xylazine
Neostigmine
Hexamethonium
Tetrodotoxin
Atropine
Isoproterenol
Acetylcholine

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "α1-Adrenoceptor activation can increase heart rate directly or decrease it indirectly through parasympathetic activation",
abstract = "The chronotropic effects of α- and β-adrenoceptor agonists were investigated in the pithed rat. The β-adrenoceptor agonist, isoprenaline, produced only a positive chronotropic response. α1-Adrenoceptor agonists, phenylephrine and amidephrine, produced positive and negative chronotropic effects. Part of the response to phenylephrine was β-mediated. A positive chronotropic response to amidephrine and phenylephrine was mediated directly through cardiac α1-adrenoceptors and had a different time course from β-adrenoceptor-mediated responses. A negative chronotropic response to α-agonists was potentiated by neostigmine and blocked by atropine, tetrodotoxin or hexamethonium as well as by α1-adrenoceptor antagonists. This may indicate α1-adrenoceptors on preganglionic parasympathetic nerves, stimulation of these receptors causing release of acetylcholine. The α2-adrenoceptor agonist, xylazine, produced a direct negative chronotropic effect on the heart, independent of α-adrenoceptors. No evidence was found for functional post-junctional α2-adrenoceptors. At high doses xylazine stimulated cardiac α1-adrenoceptors.",
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AB - The chronotropic effects of α- and β-adrenoceptor agonists were investigated in the pithed rat. The β-adrenoceptor agonist, isoprenaline, produced only a positive chronotropic response. α1-Adrenoceptor agonists, phenylephrine and amidephrine, produced positive and negative chronotropic effects. Part of the response to phenylephrine was β-mediated. A positive chronotropic response to amidephrine and phenylephrine was mediated directly through cardiac α1-adrenoceptors and had a different time course from β-adrenoceptor-mediated responses. A negative chronotropic response to α-agonists was potentiated by neostigmine and blocked by atropine, tetrodotoxin or hexamethonium as well as by α1-adrenoceptor antagonists. This may indicate α1-adrenoceptors on preganglionic parasympathetic nerves, stimulation of these receptors causing release of acetylcholine. The α2-adrenoceptor agonist, xylazine, produced a direct negative chronotropic effect on the heart, independent of α-adrenoceptors. No evidence was found for functional post-junctional α2-adrenoceptors. At high doses xylazine stimulated cardiac α1-adrenoceptors.

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