Abstract
The development and progression of heart failure (HF) due to myocardial infarction (MI) is a major concern even with current optimal therapy. Resveratrol is a plant polyphenol with cardioprotective properties. Sacubitril/valsartan is known to be beneficial in chronic HF patients. In this study, we investigated the comparative and combinatorial benefits of resveratrol with sacubitril/valsartan alongside an active comparator valsartan in MI-induced male Sprague Dawley rats. MI-induced and sham-operated animals received vehicle, resveratrol, sacubitril/valsartan, valsartan alone or sacubitril/valsartan + resveratrol for 8 weeks. Echocardiography was performed at the endpoint to assess cardiac structure and function. Cardiac oxidative stress, inflammation, fibrosis, brain natriuretic peptide (BNP), creatinine and neutrophil gelatinase associated lipocalin were measured. Treatment with resveratrol, sacubitril/valsartan, valsartan and sacubitril/valsartan + resveratrol significantly prevented left ventricular (LV) dilatation and improved LV ejection fraction in MI-induced rats. All treatments also significantly reduced myocardial tissue oxidative stress, inflammation and fibrosis, as well as BNP. Treatment with the combination of sacubitril/valsartan and resveratrol did not show additive effects. In conclusion, resveratrol, sacubitril/valsartan, and valsartan significantly prevented cardiac remodeling and dysfunction in MI-induced rats. The reduction in cardiac remodeling and dysfunction in MI-induced rats was mediated by a reduction in cardiac oxidative stress, inflammation and fibrosis.
Highlights
Sacubitril/valsartan, valsartan, resveratrol and sacubitril/valsartan + resveratrol significantly lowered lung wet-to-dry weight ratio in myocardial infarction (MI)-induced rats compared to vehicle-treated MI-induced rats
This study revealed that the stand-alone administration of resveratrol and sacubiThis study revealed that the stand-alone administration of resveratrol and sacubitril/valsartan that was commenced immediately after MI-induction and continued for tril/valsartan that was commenced immediately after MI-induction and continued for 8
The current study showed that treatment with resveratrol, sacubitril/valsartan, valsartan and the combination was associated with a lower level of brain natriuretic peptide (BNP) in MI-induced rats
Summary
The renin-angiotensin-aldosterone system (RAAS) blockade is unequivocally established as the first and foremost clinically beneficial strategy in post-myocardial infarction (MI) and heart failure (HF) therapies [1]. The natriuretic peptide (NPs) system plays an important beneficial counter-regulatory role in limiting the detrimental effects of RAAS [2,3]. The maintenance of circulating levels of NPs has been recognized as an effective strategy in HF patients. The use of a human recombinant-NP such as nesiritide to achieve this goal has met with limited success in HF patients [4,5]. Augmenting the levels of circulating NPs by blocking their degradation via pharmacological agents has become an area of keen interest in the drug therapy for HF [6,7]
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