Published Online
on August 11, 2003

A more recent version of this article appeared on August 26, 2003

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Submitted on October 3, 2002
Revised on February 28, 2003
Accepted on May 21, 2003

Comparative Effects of Carvedilol and Metoprolol on Regional Vascular Responses to Adrenergic Stimuli in Normal Subjects and Patients With Chronic Heart Failure

Katarzyna Hryniewicz MD, Ana Silvia Androne MD, Alhakam Hudaihed MD, and Stuart D. Katz MD^*

From the Department of Medicine, Columbia University College of Physicians & Surgeons, New York, NY, and Department of Internal Medicine, Yale University College of Medicine, New Haven, Conn.

^* To whom correspondence should be addressed. E-mail: stuart.katz{at}yale.edu.

Background--Adrenergic receptor blockers used in the treatment of heart failure have distinct receptor affinity profiles. We hypothesized that -adrenergic-blocking effects of carvedilol would limit vasoconstriction in response to adrenergic stimuli when compared with metoprolol.

Methods and Results--Forearm vascular resistance responses to isometric handgrip and cold pressor test were determined by plethysmography before and during adrenergic receptor blockade in prospective randomized trials. Acute effects were assessed in a crossover trial in normal subjects (single dose of 25 mg carvedilol, 100 mg metoprolol tartrate, and placebo). Chronic effects (25 mg carvedilol BID versus 200 mg extended-release metoprolol succinate daily for 6 months) were assessed in a parallel group trial of chronic heart failure subjects. In normal subjects, carvedilol decreased forearm vascular resistance responses to adrenergic stimuli when compared with metoprolol and placebo (isometric handgrip -3.5 U for carvedilol versus -1.2 U for metoprolol and -2.2 U for placebo, P=0.15; cold pressor test 3.1±8.9 U for carvedilol versus 9.0±2.7 U for metoprolol and 8.2±5.8 U for placebo, P<0.05). In heart failure subjects, vasomotor responses to isometric handgrip and cold pressor test did not differ between treatment groups.

Conclusions--Acute administration of carvedilol attenuates the vasoconstriction response to adrenergic stimuli when compared with placebo and metoprolol in normal subjects, whereas chronic administration of carvedilol does not attenuate the vasoconstrictor response to adrenergic stimuli when compared with metoprolol in heart failure subjects. These data suggest that long-term benefits of carvedilol in heart failure are not mediated by -adrenergic blockade.

Key words: heart failure • nervous system, sympathetic • vasoconstriction • pharmacology • blood flow

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