α₁-Blocking properties of carvedilol during acute and chronic administration

Carvedilol is a β-adrenergic-blocking drug with vasodilating properties. This vasodilation has been ascribed to α₁-adrenergic blockade, but it has never been shown in the clinical setting. We addressed this issue by studying eight patients with mild essential hypertension who were given prazosin, 2 mg or carvedilol, 25 mg p.o. following a 2-week washout from previous treatment, according to a randomized double-blind, crossover experimental design. Before and 2 h after the administration of either prazosin or carvedilol, the patients were infused i.v. with increasing doses of phenylephrine (0.2-1.2 μg/kg/min) and isoproterenol (0.01-0.05 μg/kg/min). The patients were thereafter maintained on carvedilol 25 mg daily for 3 weeks, and the i.v. phenylephrine and isoproterenol infusions were repeated 2 h after the last tablet administration. The results showed that the single dose of carvedilol and prazosin lowered blood pressure (beat-to-beat finger pressure measurement) to a similar extent, but that heart rate was unaffected by prazosin and reduced by carvedilol. The tachycardic response to isoproterenol was abolished by carvedilol and unaffected by prazosin, whereas the pressor response to phenylephrine was reduced by carvedilol and virtually abolished by prazosin. The antihypertensive, β-blocking and α₁-adrenergic-blocking effects of carvedilol were unchanged following prolonged administration of the drug. Thus, at a clinically effective dose, carvedilol not only has β- but also sizeable α₁-blocking effects. These effects are preserved during prolonged administration of the drug. For a comparable antihypertensive action, however, the α₁-blocking effect is less pronounced than that of an α₁-blocker such as prazosin.