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Curr Protein Pept Sci ; 23(5): 321-334, 2022.
Article in English | MEDLINE | ID: covidwho-1910825


Natriuretic peptide system (NPS) is a group of peptide hormones or paracrine factors, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and natriuretic peptide precursor C (NPC), that are structurally related. The physiological effects of NPS include natriuresis, increased glomerular filtration rate, inhibition release of renin, vasopressin, and aldosterone, sympathetic inhibition, vasodilatations, and prevents cardiac hypertrophy and remodeling. ANP has immunological effects, as it is produced locally from immune cells; it regulates innate and adaptive immune responses. Metabolism and degradation of ANP are achieved by neutral endopeptidase (NEP), also known as neprilysin. Coronavirus disease 2019 (Covid-19) pandemic may lead to acute lung injury (ALI) and/or respiratory distress syndrome (ARDS). The underlying causes of inflammatory and immunological disorders in patients with severe Covid-19 are connected to the immune over-stimulation with the subsequent release of pro-inflammatory cytokines. Covid-19 severity is linked with high ANP serum levels regardless of acute cardiac injury. Inflammatory stimuli appear to be linked with the release of NPs, which anti-inflammatory effects prevent the development of ALI/ARDS in Covid-19. Therefore, neprilysin inhibitors like sacubitril increase endogenous NPs and may reduce the risk of ALI in Covid-19 due to the potentiation of endogenous anti-inflammatory effects of NPs. However, sacubitril increases gastrin-releasing peptide, cathepsin G and release of pro-inflammatory cytokines that are inactivated by neprilysin. In conclusion, NPs and neprilysin have cardio-pulmonary protective effects against Covid-19-induced ALI/ARDS. Neprilysin inhibitor sacubitril has dual protective and harmful effects regarding metabolizing vasoactive peptides by neprilysin. These findings require potential reevaluation of the effect of neprilysin inhibitors in managing Covid-19.

COVID-19 Drug Treatment , Heart Failure , Respiratory Distress Syndrome , Aldosterone , Aminobutyrates , Anti-Inflammatory Agents , Atrial Natriuretic Factor/metabolism , Atrial Natriuretic Factor/therapeutic use , Biphenyl Compounds , Cathepsin G , Cytokines , Gastrin-Releasing Peptide/therapeutic use , Heart Failure/drug therapy , Humans , Natriuretic Peptide, Brain/metabolism , Natriuretic Peptide, Brain/therapeutic use , Natriuretic Peptides , Neprilysin/metabolism , Neprilysin/therapeutic use , Renin/therapeutic use , Tetrazoles/pharmacology , Tetrazoles/therapeutic use , Valsartan/therapeutic use
Eur Rev Med Pharmacol Sci ; 24(23): 12527-12535, 2020 12.
Article in English | MEDLINE | ID: covidwho-995013


Since December 2019, an outbreak of a new coronavirus, COVID-19, infection has been taking place. At present, COVID-19 has spread to most countries worldwide. The latest evidence suggests that cytokine storm syndrome (CSS) is an important cause of the transition from mild to critical pneumonia and critically ill patients' death. The sudden exacerbation of COVID-19 may be related to a cytokine storm. Therefore, early identification and active treatment of CSS may play very important roles in improving the patients' prognosis, and these tasks are given attention in the current treatment of new Coronavirus pneumonia. However, there is still no specific medicine for this purpose. This article reviews cytokine storms and conducts an exploratory review of pharmacotherapy for cytokine storms to provide a reference for clinical treatment.

COVID-19/immunology , Cytokine Release Syndrome/immunology , Myocarditis/immunology , Angiotensin-Converting Enzyme 2/metabolism , Antibodies, Monoclonal, Humanized/therapeutic use , Antioxidants/therapeutic use , Apoptosis , Atrial Natriuretic Factor/therapeutic use , Azetidines/therapeutic use , Benzyl Compounds/therapeutic use , Cytokine Release Syndrome/drug therapy , Enzyme Inhibitors/therapeutic use , Glucocorticoids/therapeutic use , Glycoproteins/therapeutic use , Humans , Hypoxia/metabolism , Hypoxia/therapy , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Myocardial Ischemia/metabolism , Myocarditis/metabolism , Myocarditis/therapy , Myocytes, Cardiac/metabolism , Oxidative Stress , Oxygen Inhalation Therapy , Respiration, Artificial , SARS-CoV-2 , Sphingosine 1 Phosphate Receptor Modulators/therapeutic use , Trypsin Inhibitors/therapeutic use , Tumor Necrosis Factor Inhibitors/therapeutic use , alpha-Methyltyrosine/therapeutic use , COVID-19 Drug Treatment