Mechanism of the Vasodilatory Effect of Carvedilol in Normal Volunteers: A Comparison with Labetalol

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Abstract
Summary: In a single blind parallel design, saline (n = 9), labetalol i.v. (40 mg n = 4, 80 mg n = 3), and carvedilol i.v. (15 mg n = 8) were given to volunteers with blood pressure (BP) recorded intraarterially. The effect of these treatments on the response to challenge doses of angiotensin II (to give a rise in mean BP of 20–25 mm Hg), isoproterenol (to give an increase in heart rate of 30–35 beats/min), and phenylephrine (to give a rise in mean BP of 20–25 mm Hg) were studied. The dose of i.v. carvedilol employed gave a greater fall in BP than the dose of labetalol used. Carvedilol appeared to be about four times more potent than labetalol in inhibiting the tachycardia to isoprenaline. Likewise, from inhibition of the pressor response to phenylephrine, it is concluded that carvedilol is four times more effective at the alpha receptor than labetalol. Neither drug was found to antagonize the pressor effects of angiotensin. Calculation of the half-life of carvedilol gave values of 2.2 to 9 h. The volume of distribution was found to be 1.54 1/kg and the total body clearance was 0.521 1/h/kg.

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