Ranolazine, a novel anti-anginal agent, does not alter isosorbide dinitrate- or sildenafil-induced changes in blood pressure in conscious dogs.

Abstract Effects of ranolazine on isosorbide dinitrate- and on sildenafil-induced changes in mean arterial pressure and heart rate were assessed in conscious dogs. Dogs ( n  = 7) were chronically instrumented for measurements of mean arterial pressure and heart rate. Bolus intravenous injections of either isosorbide dinitrate (0.2 mg/kg) or sildenafil (0.5 mg/kg) caused biphasic changes in mean arterial pressure and heart rate: a transient (∼ 20 s) decrease in mean arterial pressure and an increase in heart rate, followed by prolonged (10–15 min) decreases in mean arterial pressure by 11 ± 1.6 and 11 ± 2.2 mm Hg, respectively. Infusion of ranolazine alone (plasma concentrations = 4 or 8 μM) for 10 min did not significantly affect mean arterial pressure and heart rate. The transient hypotension and tachycardia caused by isosorbide dinitrate were not altered by ranolazine. The sildenafil-induced transient tachycardia (Δ change: 114 ± 10 beats/min) was significantly ( P