title: Nonselective versus selective beta-adrenergic receptor blockade in congestive heart failure: differential effects on sympathetic activity.
abstract: BACKGROUND
  Activation of the sympathetic nervous system has important prognostic implications in chronic heart failure. Nonselective versus selective beta-adrenergic receptor antagonists may have differential effects on norepinephrine release from nerve terminals mediated by prejunctional beta(2)-adrenergic receptors.
  
  
  RESULTS
  Thirty-six patients with chronic heart failure were randomized to the nonselective beta-blocker carvedilol or the selective beta-blocker metoprolol (double-blind). Measurements of hemodynamics and cardiac and systemic norepinephrine spillover as well as microneurographic recordings of muscle sympathetic nerve traffic were made before and after 4 months of therapy. In the carvedilol group (n=17), there were significant reductions in both total body (-1.7+/-0.5 nmol/min, P<0.01) and cardiac norepinephrine spillover (-87+/-29 pmol/min, P<0.01). By contrast, in the metoprolol group (n=14), there were no significant changes in total body or cardiac norepinephrine spillover. Responses in the carvedilol group were significantly different from those observed in the metoprolol group (P<0.05). Both agents caused a reduction in heart rate and increases in pulse pressure, although mean arterial pressure did not change. Importantly, microneurographic measures of sympathetic nerve traffic to skeletal muscle did not change in either group.
  
  
  CONCLUSIONS
  Therapy with carvedilol caused significant decreases in systemic and cardiac norepinephrine spillover, an indirect measure of norepinephrine release. Such changes were not observed in patients treated with metoprolol. There was no effect of either agent on sympathetic efferent neuronal discharge to skeletal muscle. These findings suggest that carvedilol, a nonselective beta-blocker, caused its sympathoinhibitory effect by blocking peripheral, prejunctional beta-adrenergic receptors.
authors.affiliation: Division of Cardiology, Department of Medicine, Mount Sinai Hospital, University of Toronto, Ontario, Winnipeg, Canada.
authors.forename: E R
authors.initials: ER
authors.lastname: Azevedo
authors.forename: T
authors.initials: T
authors.lastname: Kubo
authors.forename: S
authors.initials: S
authors.lastname: Mak
authors.forename: A
authors.initials: A
authors.lastname: Al-Hesayen
authors.forename: A
authors.initials: A
authors.lastname: Schofield
authors.forename: R
authors.initials: R
authors.lastname: Allan
authors.forename: S
authors.initials: S
authors.lastname: Kelly
authors.forename: G E
authors.initials: GE
authors.lastname: Newton
authors.forename: J S
authors.initials: JS
authors.lastname: Floras
authors.forename: J D
authors.initials: JD
authors.lastname: Parker
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000008:administration & dosage; D000077261:Carvedilol; D002908:Chronic Disease; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008790:Metoprolol / Q000008:administration & dosage; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000294:innervation; D009638:Norepinephrine / Q000378:metabolism; D011412:Propanolamines / Q000008:administration & dosage; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013379:Substrate Specificity; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D000077261:Carvedilol; D008790:Metoprolol; D009638:Norepinephrine