Effects of Calcium Channel Antagonists on Ca2+Transients in Rat and Canine Cardiomyocytes
| Autor: | J. Hensley, C. M. Hohl, Ruth A. Altschuld, J D Johnson, George E. Billman |
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| Rok vydání: | 1997 |
| Předmět: |
Male
Agonist medicine.medical_specialty Cardiotonic Agents medicine.drug_class Heart Ventricles Pharmacology Rats Sprague-Dawley Contractility Dogs Species Specificity Nifedipine Internal medicine medicine Animals Channel blocker Molecular Biology Mibefradil Dose-Response Relationship Drug Chemistry Myocardium Calcium channel Biological Transport 3-Pyridinecarboxylic acid 1 4-dihydro-2 6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)- Methyl ester Calcium Channel Blockers Electric Stimulation Rats Calcium Channel Agonists Endocrinology Felodipine Verapamil Calcium Female Cardiology and Cardiovascular Medicine medicine.drug |
| Zdroj: | Journal of Molecular and Cellular Cardiology. 29:1037-1043 |
| ISSN: | 0022-2828 |
| DOI: | 10.1006/jmcc.1996.0348 |
| Popis: | First-generation Ca 2+ channel antagonists depress myocardial contractility, but many of the newer Ca 2+ channel blockers have a high degree of “vascular selectivity”. This study compares the effects of the Ca 2+ antagonists felodipine, amlodipine, mibefradil, verapamil and nifedipine, and the Ca 2+ channel agonist, ( S )(−)-Bay K-8644 on Ca 2+ transient amplitudes in fura-2/AM-loaded rat and canine ventricular cardiomyocytes. At 10 −11 and 10 −10 m , felodipine increased [Ca 2+ ] i transient amplitudes by 10–25% in field-stimulated fura-2-loaded cells from both species while at 10 −6 m it depressed [Ca 2+ ] i transients by 80%. Mibefradil increased [Ca 2+ ] 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 [Ca 2+ ] i transient amplitudes at 10 −10 –10 −6 m (maximally 37% at 10 −7 m ) but depressed [Ca 2+ ] 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 [Ca 2+ ] i transient amplitudes by 37%. All concentrations of verapamil and amlodipine (10 −11 –10 −6 m ) depressed [Ca 2+ ] 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. |
| Databáze: | OpenAIRE |
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