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Published on: September 28, 2016
Skeletal muscle proteins oxidation in chronic right heart failure in rats: can different beta-blockers prevent it to
Luciano Dalla Libera1, Barbara Ravara, Valerio Gobbo
1CNR Institute of Neurosciences, Unit for Neuromuscular Biology and Pathophysiology, Department of Biomedical Sciences, University of Padova, Padova, Italy.
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.
Methods And 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.
Insights
Nebivolol, a nitric oxide-donating beta-blocker, shows superior effects in chronic heart failure (CHF) skeletal muscle compared to bisoprolol. It prevents muscle atrophy and protein oxidation, potentially improving exercise capacity.
Area of Science:
- Cardiovascular Medicine
- Skeletal Muscle Physiology
- Pharmacology
Background:
- Skeletal muscle atrophy and reduced slow-fiber expression impair exercise capacity in Chronic Heart Failure (CHF).
- Oxidative stress from pro-inflammatory cytokines and free radicals exacerbates muscle damage in CHF.
- Beta-blockers like carvedilol can prevent contractile protein oxidation in CHF models.
Purpose of the Study:
- To compare the effects of nebivolol (a beta-blocker with NO-donor activity) and bisoprolol on skeletal muscle in a rat model of CHF.
- To investigate potential differences impacting muscle function and exercise capacity.
Main Methods:
- Utilized the monocrotaline rat model of CHF.
- Compared nebivolol and bisoprolol treatments.
- Assessed skeletal muscle apoptosis, atrophy, sarcomeric protein composition and oxidation, and muscle efficiency.
Main Results:
- Nebivolol effectively prevented protein oxidation, while bisoprolol showed only partial prevention.
- Nebivolol significantly improved muscle twitch force production and relaxation.
- Nebivolol inhibited the shift towards fast muscle isoforms, reduced atrophy, decreased apoptosis, and lowered sphingosine levels.
Conclusions:
- Nebivolol demonstrates superior efficacy over bisoprolol in CHF skeletal muscle.
- Nebivolol reduces apoptosis and cytokine-induced muscle wasting, prevents fiber-type shift, and mitigates protein oxidation, likely via nitric oxide generation.
- These beneficial effects suggest nebivolol may positively impact exercise capacity in human CHF patients.
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