Positive chronotropic effect of Bay K 8644: participation of endogenous norepinephrine

Maria C. de Hurtado Camilion, Oscar A. Gende, Horacio E. Cingolani

Research output: Contribution to journalArticle

Abstract

The chronotropic effect of Bay K 8644, a dihydropyridine known to increase the slow inward current, was studied in spontaneously beating rat atria. Increases in atrial rate were concentration-dependent and the maximal increase (106 ± 10 beats/min) was obtained at 3 × 10−6 mol/l. Reserpine pretreatment, or propranolol 3 × 10−7 mol/l, or propranolol plus prazosin 10−6 mol/l decreased the maximum chronotropic effect of Bay K 8644 by about 60%. Blockade of the removal mechanisms of catecholamines (hydrocortisone 3 × 10−5 mol/l plus cocaine 10−5 mol/1) did not prevent the chronotropic effect of the compound. Exposure to Bay K 8644 increased the spontaneous outflow of tritium from atria preloaded with [3H]-norepinephrine by 30%. The results indicate that Bay K 8644 produces positive chronotropic effects through two mechanisms: a direct one and an indirect mechanism that involves the participation of norepinephrine released from sympathetic nerve endings.

Original languageEnglish (US)
Pages (from-to)452-455
Number of pages4
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume340
Issue number4
DOIs
StatePublished - Oct 1989

Keywords

  • Bay K 8644
  • Chronotropic response
  • Norepinephrine release
  • Rat atria

ASJC Scopus subject areas

  • Pharmacology

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