Single and repeated doses of the vasodilator/β-adrenergic antagonist, carvedilol, block cirazoline- and isoproterenol-mediated hemodynamic responses in the conscious rat

The purpose of this study was to evaluate the effects of carvedilol, a β1&2 blocker and vasodilator, on cirazoline-mediated changes in arterial blood pressure and isoproterenol-mediated changes in heart rate after acute and chronic administration. Conscious, chronically instrumented male Sprague-Dawley rats were injected with carvedilol (1 mg/kg, IV), prazosin (0.3 mg/kg, IV), or propranolol (1 mg/kg, IV) twice daily for 8 days. After administration of the first dose of carvedilol on day 1, the vasopressor response to cirazoline (60±3 mmHg predrug) and the isoproterenol-induced tachycardia (152±13 beats/min predrug) were blocked (e.g., 7±4 mmHg postdrug and 11±3 beats/min postdrug, respectively). After the administration of carvedilol on day 8, the cirazoline vasopressor response was 2±1 mmHg and the isoproterenol-induced tachycardia was 4±3 beats/min, indicating effective α- and β-adrenergic blockade after chronic dosing with carvedilol. Prazosin blocked the cirazoline-induced vasopressor response on both days 1 and 8 but had no effect on the isoproterenol-induced tachycardia. Propranolol blocked the isoproterenol-induced tachycardia on both days 1 and 8 but had no effect on the cirazoline vasopressor response. These data indicate that only carvedilol effectively blocked both α- and β-adrenergic hemodynamic responses and that the antagonism of these responses with carvedilol was not diminished after chronic dosing of twice-a-day treatment for 8 days.