title: Skeletal muscle proteins oxidation in chronic right heart failure in rats: can different beta-blockers prevent it to the same degree?
abstract: BACKGROUND
  Skeletal muscle atrophy and decreased expression of slow fibers contribute to exercise capacity limitation in Chronic Heart Failure (CHF). Pro-inflammatory cytokines and free radicals worsen muscle damage. In CHF sarcomeric proteins are oxidized with reduction of muscle twitch efficiency, and VO(2)-max. Beta-blockers with anti-oxidative capacity such as carvedilol have been shown to prevent contractile protein oxidation in CHF rats. Recently a new class of beta-blockers with NO donor activity has been introduced and approved for the treatment of CHF. Since a clinical clear superiority of a beta-blocker has never been shown, we compared nebivolol, that possesses NO donor activity, with bisoprolol, looking at possible differences in skeletal muscle that may have an impact on muscle function and exercise capacity in humans. We therefore studied skeletal muscle apoptosis and wastage, sarcomeric protein composition and oxidation, and muscle efficiency.
  
  
  RESULTS
  In the monocrotaline rat model of CHF we compared nebivolol a beta-blocker with vasodilative properties mediated by NO production, with bisoprolol. Nebivolol prevented protein oxidation, while bisoprolol did it only partially, as demonstrated by the oxyblot analysis (Oxy/RP values) (0.90+/-0.14 Controls.; 1.7+/-0.14 CHF; 1.1+/-0.05 bisoprolol; 0.82+/-0.17 nebivolol low; 0.62+/-0.10 nebivolol high). Only nebivolol improved twitch force production and relaxation. Nebivolol prevented fibers shift towards fast isoforms, atrophy, decreased apoptosis and sphingosine levels.
  
  
  CONCLUSIONS
  Nebivolol seems better than bisoprolol in CHF by decreasing apoptosis and cytokines induced muscle wastage, preventing fibers shift and protein oxidation. Nebivolol by stimulating NO generation may have prevented protein oxidation. It could be speculated that ROS release, pro-inflammatory cytokines production and NF-kappa-B activation may play a key role. These positive changes could produce a favorable impact on exercise capacity in man.
authors.affiliation: CNR Institute of Neurosciences, Unit for Neuromuscular Biology and Pathophysiology, Department of Biomedical Sciences, University of Padova, Padova, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Dalla Libera
authors.forename: Barbara
authors.initials: B
authors.lastname: Ravara
authors.forename: Valerio
authors.initials: V
authors.lastname: Gobbo
authors.forename: Daniela Danieli
authors.initials: DD
authors.lastname: Betto
authors.forename: Elena
authors.initials: E
authors.lastname: Germinario
authors.forename: Annalisa
authors.initials: A
authors.lastname: Angelini
authors.forename: Stefano
authors.initials: S
authors.lastname: Evangelista
authors.forename: Giorgio
authors.initials: G
authors.lastname: Vescovo
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology*; D017298:Bisoprolol / Q000494:pharmacology; D002908:Chronic Disease; D004983:Ethanolamines / Q000494:pharmacology*; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000068577:Nebivolol; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012518:Sarcomeres / Q000187:drug effects / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D009124:Muscle Proteins; D000068577:Nebivolol; D017298:Bisoprolol