Ranolazine Attenuates Palmitoyl-l -carnitine-induced Mechanical and Metabolic Derangement in the Isolated, Perfused Rat Heart
| Autor: | Hiroko Hashizume, Fumitaka Ushikubi, Akiyoshi Hara, Yasushi Abiko, Kazuyasu Maruyama |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Adenosine monophosphate medicine.medical_specialty Ischemia Pharmaceutical Science Ranolazine Pyruvate Dehydrogenase Complex In Vitro Techniques Piperazines Ventricular Function Left Rats Sprague-Dawley chemistry.chemical_compound Adenosine Triphosphate Carnitine Internal medicine Animals Medicine Enzyme Inhibitors Pharmacology business.industry Activator (genetics) Heart medicine.disease Pyruvate dehydrogenase complex Rats Endocrinology Mechanism of action chemistry Acetanilides medicine.symptom business Adenosine triphosphate medicine.drug |
| Zdroj: | Journal of Pharmacy and Pharmacology. 52:709-715 |
| ISSN: | 2042-7158 0022-3573 |
| DOI: | 10.1211/0022357001774381 |
| Popis: | The effect of ranolazine, a novel anti-ischaemic drug that stimulates the activity of pyruvate dehydrogenase, on palmitoyl-l-carnitine-induced mechanical dysfunction and metabolic derangement in isolated perfused rat hearts has been studied and compared with the effect of dichloroacetate, an activator of pyruvate dehydrogenase. Rat hearts paced electrically were perfused aerobically at constant flow by the Langendorff technique. Palmitoyl-l-carnitine (4 μm) increased left ventricular end-diastolic pressure and reduced left ventricular developed pressure (i.e. induced mechanical dysfunction); it also reduced tissue levels of adenosine triphosphate and increased tissue levels of adenosine monophosphate (i.e. induced metabolic derangement). These functional and metabolic alterations induced by palmitoyl-l-carnitine were attenuated by ranolazine (5, 10, and 20 μm) in a concentration-dependent manner. In contrast, dichloroacetate (1 and 10 mm) did not attenuate palmitoyl-l-carnitine-induced mechanical and metabolic derangement. In the normal (palmitoyl-l-carnitine-untreated) heart, however, ranolazine did not modify mechanical function and energy metabolism. These results suggest that ranolazine attenuates palmitoyl-l-carnitine-induced mechanical and metabolic derangement in the rat heart, and that the beneficial action of ranolazine is not because of the energy-sparing effect or activation of pyruvate dehydrogenase. |
| Databáze: | OpenAIRE |
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