Electrophysiological basis for the bradycardic effects of 1-(1-pyrrolidinylmethyl)-2-naphthol in rodents

Chin J Physiol. 1992;35(1):45-54.

Abstract

In anesthetized rats, intravenous injection of 1-(1-pyrrolidinylmethyl)-2-naphthol (TPY-beta, 0.1-1 mg/kg) induced a transient (less than 1 min) decrease in arterial blood pressure and heart rate (acute responses) followed by a delayed and sustained (greater than 10 min) bradycardic response. The electrophysiological mechanisms responsible for the bradycardic effect of TPY-beta were studied in sinoatrial tissues isolated from guinea-pig hearts. Transmembrane action potential (AP) and twitch force of atrial tissues were recorded with the conventional microelectrode techniques. In sinoatrial pacemakers active spontaneously in 4 mM [K]o Tyrode solution, TPY-beta (3-100 microM) depressed the diastolic slope and the rate of spontaneous discharges. When the non-automatic atrial tissues were driven at a fixed rate, TPY-beta (10-100 microM) inhibited the upstroke velocity of phase-0 depolarization and prolonged AP duration. In atrial fibers depolarized in high [K]o (24 mM), TPY-beta depressed the phase-0 upstroke of slow response AP and the twitch force in a concentration-dependent manner. The present results indicate that TPY-beta induced direct negative chronotropic and inotropic effects on guinea-pig atrial pacemakers and myocardial fibers. The underlying mechanisms involve a general inhibition of transmembrane of Ca, K and Na ion fluxes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Blood Pressure / drug effects
  • Calcium Channels / drug effects
  • Cardiovascular Agents / pharmacology*
  • Depression, Chemical
  • Female
  • Guinea Pigs
  • Heart Rate / drug effects*
  • In Vitro Techniques
  • Male
  • Naphthols / pharmacology*
  • Potassium Channels / drug effects
  • Pyrrolidines / pharmacology*
  • Rats
  • Rats, Inbred Strains

Substances

  • Calcium Channels
  • Cardiovascular Agents
  • Naphthols
  • Potassium Channels
  • Pyrrolidines
  • 1-(1-pyrrolidinylmethyl)-2-naphthol