scholarly journals The Rationale for Angiotensin Receptor Neprilysin Inhibitors in a Multi-Targeted Therapeutic Approach to COVID-19

2020 ◽  
Vol 21 (22) ◽  
pp. 8612
Author(s):  
Alessandro Bellis ◽  
Ciro Mauro ◽  
Emanuele Barbato ◽  
Bruno Trimarco ◽  
Carmine Morisco
Keyword(s):  
Positive Impact ◽  
Renin Angiotensin System ◽  
Therapeutic Strategies ◽  
Organ Injury ◽  
Lung Fibroblasts ◽  
Angiotensin Receptor ◽  
Potential Benefits ◽  
Thrombotic Complications ◽  
Selective Therapy ◽  
Targeted Therapeutic

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) determines the angiotensin converting enzyme 2 (ACE2) down-regulation and related decrease in angiotensin II degradation. Both these events trigger “cytokine storm” leading to acute lung and cardiovascular injury. A selective therapy for COVID-19 has not yet been identified. Clinical trials with remdesivir gave discordant results. Thus, healthcare systems have focused on “multi-targeted” therapeutic strategies aiming at relieving systemic inflammation and thrombotic complications. No randomized clinical trial has demonstrated the efficacy of renin angiotensin system antagonists in reducing inflammation related to COVID-19. Dexamethasone and tocilizumab showed encouraging data, but their use needs to be further validated. The still-controversial efficacy of these treatments highlighted the importance of organ injury prevention in COVID-19. Neprilysin (NEP) might be an interesting target for this purpose. NEP expression is increased by cytokines on lung fibroblasts surface. NEP activity is elevated in acute respiratory distress syndrome and it is conceivable that it is also high in COVID-19. NEP is implicated in the degradation of natriuretic peptides, bradykinin, substance P, adrenomedullin, and apelin that account for prevention of organ injury. Thus, NEP/angiotensin receptor type 1 (AT1R) inhibitor sacubitril/valsartan (SAC/VAL) may increase levels of these molecules and block AT1Rs required for ACE2 endocytosis in SARS-CoV-2 infection. Moreover, SAC/VAL has a positive impact on acute heart failure that is very frequently observed in deceased COVID-19 patients. The current review aims to summarize actual therapeutic strategies for COVID-19 and to examine the data supporting the potential benefits of SAC/VAL in COVID-19 treatment.

scholarly journals Effect of Dual Blockade of Renin-Angiotensin System on Proteinuria

2013 ◽  
Vol 1 (1) ◽  
pp. 18-20
Author(s):  
Eqerem Hasani ◽  
Alma Idrizi ◽  
Myftar Barbullushi
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Angiotensin Receptor Blocker ◽  
Enzyme Inhibitor ◽  
Combined Therapy ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin Receptor ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Dual Blockade

Aim: Aim of the study was the evaluation of the effect of dual blockade of the renin-angiotensin system (RAS) on proteinuria. Material and Methods: Sixty patients, included in the study, were treated with angiotensin-converting enzyme inhibitor and angiotensin receptor blocker for a period of 3 months. Results: The dual blockade of RAS resulted with decrease of proteinuria, a slight increase of serum creatinine and was not associated with a lowering of blood pressure.Conclusion: Combined therapy with ACE-I and ARB results in a more complete blockade of the RAS than monotherapy. In proteinuric nephropathies it reduces significantly baseline proteinuria.

scholarly journals Roles of citrus secondary metabolites in tree and fruit defence against pests and pathogens

2021 ◽  
Vol 1 (2) ◽  
pp. 51-62
Author(s):  
Ibrahim Kahramanoglu ◽  
Serhat Usanmaz
Keyword(s):  
Secondary Metabolites ◽  
Human Health ◽  
Caffeic Acid ◽  
Positive Impact ◽  
Plant Defence ◽  
Background Information ◽  
Diverse Group ◽  
Coumaric Acid ◽  
Horticultural Crops ◽  
Potential Benefits

Plants have evolved several mechanisms to protect themselves from different biotic and abiotic challenges, including pest and pathogen attacks. One of the most important mechanisms is the secondary metabolites (SM) (terpenes, phenolics and nitrogen/sulphur-containing compounds). The plants have synthesised a diverse group of compounds in different concentrations (mostly in very small quantities) and have important roles in plant defence, survival, adaptation, and reproduction. Citrus crops are among the most essential cultivated fruit groups and are rich in terpenoids and phenolics. Besides the well-known benefits of these compounds on human health, they have a significant role in plant/fruit defence against biotic and abiotic challenges. This review aims to highlight the importance of these compounds (such as limonene, citral, saponin, hesperidin, quercetin, tangeritine, caffeic acid, p-coumaric acid, scoparone, etc.) and discuss their roles in tree and fruit defence against pests and pathogens. In today’s world, where there is an essential human impact on nature, a need is raised to reduce pesticides against pests and pathogens. Therefore, understanding the roles of these SM and their induction is believed to have a significant positive impact on the production and/or storage of horticultural crops and may help reduce the use of synthetic agrochemicals. In line with this information, present review was aimed to provide a background information for researchers, farmers, horticulturalists and technology developers about the potential benefits of SM on plant/fruit defence and a guideline about their induction.

scholarly journals Evaluation of anticonvulsant activity of angiotensin receptor antagonists in an animal model

2020 ◽  
Vol 10 (1) ◽  
pp. 29
Author(s):  
Asha D. Jadhav ◽  
Rakesh R. Jadhav ◽  
Sudhir L. Padwal ◽  
Swapnil S. Jadhav ◽  
Anand S. Kale ◽  
...  
Keyword(s):  
Anticonvulsant Activity ◽  
Motor Impairment ◽  
Renin Angiotensin System ◽  
Screen Test ◽  
Angiotensin Receptor ◽  
Receptor Antagonists ◽  
Angiotensin Receptor Antagonists ◽  
Significant Prolongation ◽  
Chronic Disorder ◽  
At1 Receptor Antagonists

Background: Epilepsy is common chronic disorder in clinical practice and there was some studies which shows brain renin angiotensin system may be involved in upregulation of seizures hence present study was planned to investigate whether angiotensin II AT1 receptor antagonists possess anticonvulsant activity in experimental animals.Methods: The anticonvulsant activity of angiotensin receptor antagonists, losartan (50 mg/kg), telmisartan (30 mg/kg) and candesartan (20 mg/kg), were administered intraperitoneally to the mice and evaluated by using maximum electroshock (MES) and pentylenetetrazol induced seizures (PTZ) seizure methods. The standard was taken as phenytoin for MES and diazepam for PTZ method. Motor impairment of performance was assessed by the inverted screen test and spontaneous motor activity with digital actophotometer.Results: Losartan demonstrated the anticonvulsant efficacy in MES and PTZ models. Telmisartan and candesartan have anticonvulsant activity in MES induced seizures, but did not show protection against pentylenetetrazol induced seizures. Losartan at dose 50 mg/kg prolonged the mean latency to convulsion (p<0.01) and mean number of convulsions also significantly reduced (p<0.05) convulsions in the mice. Telmisartan and candesartan at dose 30 mg/kg and 20 mg/kg respectively showed significant prolongation in mean latency to convulsion (p<0.05). None of the test drugs i.e. angiotensin receptor antagonists showed significant motor impairment.Conclusions: Angiotensin receptor antagonists: losartan, telmisartan and candesartan had showed anticonvulsant activity in PTZ and MES seizure methods. The exact mechanism of action of their anticonvulsant action not precisely known and hence there is more studies need to test it in various other animal anticonvulsant models.

scholarly journals Functional expression of the renin-angiotensin system in human podocytes

2006 ◽  
Vol 290 (3) ◽  
pp. F710-F719 ◽  
Author(s):  
Max C. Liebau ◽  
D. Lang ◽  
J. Böhm ◽  
N. Endlich ◽  
Martin J. Bek ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Functional Expression ◽  
Kidney Cortex ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Angiotensin Receptor ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Beneficial Effects ◽  
Glomerular Proteinuria

Experimental and clinical studies impressively demonstrate that angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) significantly reduce proteinuria and retard progression of glomerular disease. The underlying intraglomerular mechanisms are not yet fully elucidated. As podocyte injury constitutes a critical step in the pathogenesis of glomerular proteinuria, beneficial effects of ACEI and ARB may partially result from interference with a local renin-angiotensin system (RAS) in podocytes. The knowledge of expression and function of a local RAS in podocytes is limited. In this study, we demonstrate functional expression of key components of the RAS in differentiated human podocytes: podocytes express mRNA for angiotensinogen, renin, ACE type 1, and the AT1 and AT2 angiotensin receptor subtypes. In Western blot experiments and immunostainings, expression of the AT1 and AT2 receptor was demonstrated both in differentiated human podocytes and in human kidney cortex. ANG II induced a concentration-dependent increase in cytosolic Ca2+ concentration via AT1 receptors in differentiated human podocytes, whereas it did not increase cAMP. Furthermore, ANG II secretion was detected, which was blocked by neither the ACEI captopril nor the renin inhibitor remikiren nor the chymase inhibitor chymostatin. ANG II secretion of podocytes was not increased by mechanical stress. Finally, ANG II was found to increase staurosporine-induced apoptosis in podocytes. We speculate that ACEI and ARB exert their beneficial effects, in part, by interfering with a local RAS in podocytes. Further experiments are required to identify the underlying molecular mechanism(s) of podocyte protection.

Shift of conventional paradigm of heart failure treatment: from angiotensin receptor neprilysin inhibitor to sodium–glucose co-transporter 2 inhibitors?

2021 ◽  
Vol 17 (3) ◽  
pp. 497-506
Author(s):  
Alexander E Berezin ◽  
Alexander A Berezin
Keyword(s):  
Heart Failure ◽  
Wide Spectrum ◽  
Large Body ◽  
Renin Angiotensin System ◽  
Angiotensin Receptor ◽  
Heart Failure Treatment ◽  
Angiotensin System ◽  
Reduced Ejection Fraction ◽  
Neprilysin Inhibitor ◽  
Angiotensin Receptor Neprilysin Inhibitor

Current clinical guidelines for heart failure (HF) contain a brand new therapeutic strategy for HF with reduced ejection fraction (HFrEF), which is based on neurohumoral modulation through the use of angiotensin receptor neprilysin inhibitors. There is a large body of evidence for the fact that sodium-glucose co-transporter 2 inhibitors may significantly improve all-cause mortality, cardiovascular mortality and hospitalization for HF in patients with HFrEF who received renin–angiotensin system blockers including angiotensin receptor neprilysin inhibitors, β-blockers and mineralocorticoid receptor antagonists. The review discusses that sodium-glucose co-transporter 2 inhibitors have a wide spectrum of favorable molecular effects and contribute to tissue protection, improving survival in HFrEF patients.

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