Anti-Adrenergic and Hemodynamic Effects of Ranolazine in Conscious Dogs Zhao, Anti-Adrenergic Effect of Ranolazine
| Autor: | Zhao, Gong, Walsh, Erin, Shryock, John, Messina, Eric, Wu, Yuzhi, Zeng, Dewan, Xu, Xiaobin, Ochoa, Manuel, Baker, Stephen, Hintze, Thomas, Belardinelli, Luiz |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Adrenergic Antagonists
Dose-Response Relationship Drug Ganglionic Blockers Vasodilator Agents Guinea Pigs Hemodynamics Isoproterenol Receptors Adrenergic alpha Autonomic Agents Hexamethonium Article Piperazines Rats Kinetics Phenylephrine Dogs Heart Rate Ranolazine Coronary Circulation Hypertension Receptors Adrenergic beta Animals Vasoconstrictor Agents Acetanilides Hypotension |
| Popis: | Effects of ranolazine alone and in the presence of phenylephrine (PE) or isoproterenol (ISO) on hemodynamics, coronary blood flow and heart rate (HR) in the absence and presence of hexamethonium (a ganglionic blocker) were studied in conscious dogs. Ranolazine (0.4, 1.2, 3.6, and 6 mg/kg, intravenous) alone caused transient (1 minute) and reversible hemodynamic changes. PE (0.3-10 μg/kg) caused a dose-dependent increase in blood pressure and decrease in HR. ISO (0.01-0.3 μg/kg) caused a dose-dependent decrease in blood pressure and an increase in HR. Ranolazine at high (11-13 mM), but not at moderate (4-5 mM) concentrations partially attenuated changes in mean arterial blood pressure and HR caused by either PE or ISO in normal conscious dogs. However, in dogs treated with hexamethonium (20 mg/kg) to cause autonomic blockade, ranolazine (both 4-5 and 11-13 μM) significantly attenuated both the PE- and ISO-induced changes in mean arterial blood pressure. The results suggest that a potential antiadrenergic effect of ranolazine was masked by autonomic control mechanisms in conscious dogs but could be observed when these mechanisms were inhibited (eg, in the hexamethonium-treated dog). Ranolazine, at plasma concentrations10 μM and in conscious dogs with intact autonomic regulation, had minimal antiadrenergic (α and β) effects. |
| Databáze: | OpenAIRE |
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