Abstract
Electrophysiological investigations of histamine in different cardiac tissues have led to the following results:
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1)
Histamine and the H2-agonists dimaprit and impromidine show similar actions on electrophysiological parameters of ventricular myocardium (especially a decrease in action potential duration), which are completely blocked by cimetidine and enhanced by the phosphodiesterase inhibitor 1-methyl,3-isobutylxanthine (IBMX). These effects may be explained by an increase in cellular cAMP leading to an increase in slow inward current and outward currents as shown by voltage clamp experiments.
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2)
Histamine in contrast to IBMX increases action potential duration at 90% repolarization (APD90) in atria. Histamine effects in atrial myocardium are completely reversed by the H1-antagonist dimetindene. Stimulation of atrial H1-receptors is suggested to directly cause an increase in Ca-channel conductance independent of intracellular cAMP content.
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3)
Histamine reduces AH-interval, increases\(\dot V_{max} \) of NH — cells and may induce AV — node arrhythmias (at concentrations ≥ 3 μmol/l). These effects remain unchanged by dimetindene, but are reversed by cimetidine. The results indicate that histamine increases AV — nodal conduction via H2-receptors.
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4)
Unspecific membrane actions of cimetidine are not observed up to 100 μmol/l. Dimetindene increases action potential duration (APD) in left atria and decreases\(\dot V_{max} \) at concentrations ≥ 10 μmol/l. However, H1-antagonistic actions of dimetindene are already observed at concentrations 1,000 to 10,000 times lower (pA2—values 8.39–9.12) so that unspecific membrane actions are suggested not to occur on a therapeutic dose level.
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Supported by the Deutsche Forschungsgemeinschaft, SFB 30, Cardiology.
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Borchard, U., Hafner, D. & Hirth, C. Electrophysiological actions of histamien and H1-,H 2-receptor antagonists in cardiac tissue . Agents and Actions 18, 186–190 (1986). https://doi.org/10.1007/BF01988017
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DOI: https://doi.org/10.1007/BF01988017