Antiadrenergic and hemodynamic effects of ranolazine in conscious dogs

Gong Zhao, Erin Walsh, John C. Shryock, Eric Messina, Yuzhi Wu, Dewan Zeng, Xiaobin Xu, Manuel Ochoa, Stephen P. Baker, Thomas H. Hintze, Luiz Belardinelli

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

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 1/4g/kg) caused a dose-dependent increase in blood pressure and decrease in HR. ISO (0.01-0.3 1/4g/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 1/4M) 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 concentrations <10 1/4M and in conscious dogs with intact autonomic regulation, had minimal antiadrenergic (± and 2) effects.

Original languageEnglish
Pages (from-to)639-647
Number of pages9
JournalJournal of Cardiovascular Pharmacology
Volume57
Issue number6
DOIs
StatePublished - Jun 2011
Externally publishedYes

Keywords

  • antiadrenergic effect
  • conscious dogs
  • coronary blood flow
  • hemodynamics
  • ranolazine

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