Electrophysiological basis for the bradycardic effects of 1-(1-pyrrolidinylmethyl)-2-naphthol in rodents.
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.
Shen
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Department of Biomedical Sciences, Foo Yin Junior College of Nursing and Medical Technology, Kaohsiung County, Taiwan, Republic of China.
Chen
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Lin
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015220:Calcium Channels / Q000187:drug effects; D002317:Cardiovascular Agents / Q000494:pharmacology*; D003864:Depression, Chemical; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009284:Naphthols / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D015220:Calcium Channels; D002317:Cardiovascular Agents; D009284:Naphthols; D015221:Potassium Channels; D011759:Pyrrolidines; C078025:1-(1-pyrrolidinylmethyl)-2-naphthol