A Novel Paradigm for Sacubitril/Valsartan: Beta-Endorphin Elevation as a Contributor to Exercise Tolerance Improvement in Rats With Preexisting Heart Failure Induced by Pressure Overload

Maslov, Mikhail Y.; Foianini, Stephan; Orlov, Michael V.; Januzzi, James L.; Lovich, Mark A.

doi:10.1016/j.cardfail.2018.10.006

Cited by 17 publications

(14 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reports from previous studies are conflicting, where some show increased circulating levels while others do not. 11,29,33 A previous human trial by Kobalava et al did not find an increase in circulating ANP with administration of sac/val twice daily, 34 while Nougue et al found an increase in circulating ANP as measured by MS/MS. 35 The lack of an increase in our data could indicate that circulating levels of ANP and BNP do not necessarily rise with NEPi in all disease states, depending on baseline production.…”

Section: Discussionmentioning

confidence: 93%

“…Our model was characterized by increased fibrosis, where neither treatment with sac/val nor valsartan attenuated these adverse changes. Anti-fibrotic effect of sac/val has been shown in rats previously 9,11,23 ; however, several of these observations were made in animals with HFrEF, a condition where beneficial effects of ARNi have been established in patients. Our model is closer to an HFpEF state, and the lack of impact on fibrosis could reflect a differential treatment effect between disease models with reduced and preserved EF.…”

Section: Discussionmentioning

confidence: 99%

“…They found that fibrosis, hypertrophy, and systolic dysfunction were more ameliorated by sac/val compared with valsartan alone and related these beneficial effects to restoration of PKG signalling 10 . However, Maslov et al did not find superior reduction of hypertrophy nor preservation of systolic function in a supra‐renal banding model of pressure overload in rats, 11 highlighting the need for further studies to investigate the effects of sac/val in the setting of pressure overload. Therefore, the objective of the current study was to investigate the differential effects of sac/val and valsartan alone after ascending aortic banding (AB) in rats.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Sacubitril/valsartan ameliorates cardiac hypertrophy and preserves diastolic function in cardiac pressure overload

et al. 2021

View full text Add to dashboard Cite

Aims Sacubitril/valsartan (sac/val) has shown superior effect compared with blockade of the renin-angiotensin-aldosterone system in heart failure with reduced ejection fraction. We aimed to investigate effects of sac/val compared with valsartan in a pressure overload model of heart failure with preserved ejection fraction (HFpEF). Methods and results Sprague-Dawley rats underwent aortic banding or sham (n = 16) surgery and were randomized to sac/val (n = 28), valsartan (n = 29), or vehicle (n = 26) treatment for 8 weeks. Sac/val reduced left ventricular weight by 11% compared with vehicle (P = 0.01) and 9% compared with valsartan alone (P = 0.04). Only valsartan reduced blood pressure compared with sham (P = 0.02). Longitudinal early diastolic strain rate was preserved in sac/val compared with sham, while it was reduced by 23% in vehicle (P = 0.03) and 24% in valsartan (P = 0.02). Diastolic dysfunction, measured by E/e'SR, increased by 68% in vehicle (P < 0.01) and 80% in valsartan alone (P < 0.001), while sac/val showed no increase. Neither sac/val nor valsartan prevented interstitial fibrosis. Although ejection fraction was preserved, we observed mild systolic dysfunction, with vehicle showing a 28% decrease in longitudinal strain (P < 0.01). Neither sac/val nor valsartan treatment improved this dysfunction. Conclusions In a model of HFpEF induced by cardiac pressure overload, sac/val reduced hypertrophy compared with valsartan alone and ameliorated diastolic dysfunction. These effects were independent of blood pressure. Early systolic dysfunction was not affected, supporting the notion that sac/val has the largest potential in conditions characterized by reduced ejection fraction. Observed anti-hypertrophic effects in preserved ejection fraction implicate potential benefit of sac/val in the clinical setting of hypertrophic remodelling and impaired diastolic function.

show abstract

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sacubitril/valsartan ameliorates cardiac hypertrophy and preserves diastolic function in cardiac pressure overload

et al. 2021

View full text Add to dashboard Cite

show abstract

“…ARNIs, such as sacubitril/valsartan (LCZ696), therefore, combine NEP inhibition with blockade of AT II receptor. Use of this drug has shown improvement of cardiac function, reversal of cardiac remodeling, improvement of exercise capacity, and, most importantly, reduction of cardiovascular mortality and hospitalizations in HF patients [1]. Improvement in exercise tolerance with the use of sacubitril/valsartan in an experimental setting is likely due to noncardiac mechanisms involving neurologic and endocrinologic pathways.…”

mentioning

confidence: 99%

“…It is found that sacubitril/valsartan therapy increases beta-endorphin (BE) concentrations and improves exercise tolerance. BE elevation might be a potential mechanism of action leading to improvement in exercise tolerance seen with sacubitril/valsartan [1]. HF is common after acute myocardial infarction (MI).…”

mentioning

confidence: 99%

Sacubitril/valsartan averts post-myocardial infarction ventricular remodeling and preserves heart function

Hajra

Ujjawal

Sud

et al. 2019

IJC Heart & Vasculature

View full text Add to dashboard Cite

Exercise: a molecular tool to boost muscle growth and mitochondrial performance in heart failure?

Nijholt

Sánchez-Aguilera

Voorrips

et al. 2022

European J of Heart Fail

View full text Add to dashboard Cite

Impaired exercise capacity is the key symptom of heart failure (HF) and is associated with reduced quality of life and higher mortality rates. Unfortunately, current therapies, although generally lifesaving, have only small or marginal effects on exercise capacity. Specific strategies to alleviate exercise intolerance may improve quality of life, while possibly improving prognosis as well. There is overwhelming evidence that physical exercise improves performance in cardiac and skeletal muscles in health and disease. Unravelling the mechanistic underpinnings of exercise-induced improvements in muscle function could provide targets that will allow us to boost exercise performance in HF. With the current review we discuss: (i) recently discovered signalling pathways that govern physiological muscle growth as well as mitochondrial quality control mechanisms that underlie metabolic adaptations to exercise; (ii) the mechanistic underpinnings of exercise intolerance in HF and the benefits of exercise in HF patients on molecular, functional and prognostic levels; and (iii) potential molecular therapeutics to improve exercise performance in HF. We propose that novel molecular therapies to boost adaptive muscle growth and mitochondrial quality control in HF should always be combined with some form of exercise training.

show abstract

A Novel Paradigm for Sacubitril/Valsartan: Beta-Endorphin Elevation as a Contributor to Exercise Tolerance Improvement in Rats With Preexisting Heart Failure Induced by Pressure Overload

Cited by 17 publications

References 35 publications

Sacubitril/valsartan ameliorates cardiac hypertrophy and preserves diastolic function in cardiac pressure overload

Sacubitril/valsartan ameliorates cardiac hypertrophy and preserves diastolic function in cardiac pressure overload

Sacubitril/valsartan averts post-myocardial infarction ventricular remodeling and preserves heart function

Exercise: a molecular tool to boost muscle growth and mitochondrial performance in heart failure?

Contact Info

Product

Resources

About