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Effects of calcium channel antagonists on Ca2+ transients in rat and canine cardiomyocytes.
Hensley, J; Billman, G E; Johnson, J D; Hohl, C M; Altschuld, R A.
Afiliación
  • Hensley J; Department of Medical Biochemistry, Ohio State University College of Medicine, Columbus 43210-1218, USA.
J Mol Cell Cardiol ; 29(3): 1037-43, 1997 Mar.
Article en En | MEDLINE | ID: mdl-9152864
First-generation Ca2+ channel antagonists depress myocardial contractility, but many of the newer Ca2+ channel blockers have a high degree of "vascular selectivity". This study compares the effects of the Ca2+ antagonists felodipine, amlodipine, mibefradil, verapamil and nifedipine, and the Ca2+ channel agonist. (S)(-)-Bay K-8644 on Ca2+ transient amplitudes in fura-2/AM-loaded rat and canine ventricular cardiomyocytes. At 10(-11) and 10(-10) M, felodipine increased [Ca2+]i transient amplitudes by 10-25% in field-stimulated fura-2-loaded cells from both species while at 10(-6) M it depressed [Ca2+]i transients by 80%. Mibefradil increased [Ca2+]i transient amplitudes by 16% at 10(-11) and 10(-10) M and decreased the transients by 25% at 10(-6) M. The calcium channel agonist, (S)(-)-Bay K-8644 increased [Ca2+]i transient amplitudes at 10(-10)-10(-6) M (maximally 37% at 10(-7) M) but depressed [Ca2+]i transients by 10% at 10(-5) M. Nifedipine was inhibitory at all concentrations tested (10(-11)-10(-6) M) in canine myocytes, but in rat cells. 10(-10) M nifedipine increased [Ca2+]i transient amplitudes by 37%. All concentrations of verapamil and amlodipine (10(-11)-10(-6) M) depressed [Ca2+]i transients in both rat and canine myocytes. We conclude that: (1) felodipine and mibefradil may be positive rather than negative inotropes at low concentrations, which are therapeutically relevant: and (2) low concentrations of nifedipine may have a positive inotropic effect in the rat but not the dog heart.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bloqueadores de los Canales de Calcio / Cardiotónicos / Calcio / Ventrículos Cardíacos Límite: Animals Idioma: En Revista: J Mol Cell Cardiol Año: 1997 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bloqueadores de los Canales de Calcio / Cardiotónicos / Calcio / Ventrículos Cardíacos Límite: Animals Idioma: En Revista: J Mol Cell Cardiol Año: 1997 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido