Comparative effects of carvedilol and metoprolol on regional vascular responses to adrenergic stimuli in normal subjects and patients with chronic heart failure.
BACKGROUND
Adrenergic receptor blockers used in the treatment of heart failure have distinct receptor affinity profiles. We hypothesized that alpha-adrenergic-blocking effects of carvedilol would limit vasoconstriction in response to adrenergic stimuli when compared with metoprolol.


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 alpha-adrenergic blockade.
Hryniewicz
Katarzyna
K
Department of Medicine, Columbia University College of Physicians & Surgeons, New York, NY, USA.
Androne
Ana Silvia
AS
Hudaihed
Alhakam
A
Katz
Stuart D
SD
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D009320:Atrial Natriuretic Factor / Q000097:blood; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015444:Exercise; D005260:Female; D005542:Forearm / Q000098:blood supply; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply; D020097:Natriuretic Peptide, Brain; D009638:Norepinephrine / Q000097:blood; D011412:Propanolamines / Q000494:pharmacology*; D011446:Prospective Studies; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D008790:Metoprolol; D009638:Norepinephrine