The purpose of this study was to evaluate the effects of
carvedilol, a beta 1&2-
adrenergic 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, 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 alpha 1- and beta-
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 alpha- and beta-
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.