BRADYKININ

DrugBank ID: db12126
DrugCentral: bradykinin
Synonymous :l-bradykinin


Drug Sentece Context


Table 1. Analysis of context sentence of bradykinin gene in 39 abstracts.

pmid sentence
32337769 This overreaction is probably mediated through the bradykinin receptor activation. […] Noscapine, a medication used for the treatment of cough, has been shown to inhibit bradykinin enhanced cough response in man.
32338605 We propose that this is due to a local vascular problem because of activation of bradykinin 1 receptor (B1R) and B2R on endothelial cells in the lungs. […] SARS-CoV-2 enters the cell via ACE2 that next to its role in RAAS is needed to inactivate des-Arg9 bradykinin, the potent ligand of the B1R.
32359101 In this paper, we use established and emerging evidence to propose a testable hypothesis that, a vicious positive feedback loop of des-Arg(9)-bradykinin- and bradykinin-mediated inflammation → injury → inflammation, likely precipitates life threatening respiratory complications in COVID-19.
32376099 The ACEIs are associated with cough secondary to accumulation of bradykinin and angioedema, and withdrawal rates due to adverse events are lower with ARBs.
32405877 We searched the recent literature (PubMed) on complement and coronavirus; contact system and coronavirus; bradykinin and coronavirus; and angiotensin receptor and coronavirus. […] Some evidence suggests that the observed pulmonary edema may be bradykinin-induced and could be the reason that corticosteroids, antihistamines, and other traditional interventions for edema are not effective. […] Activation of complement and the contact system, through generation of bradykinin, may play a role in the SARS-CoV-2-induced pulmonary edema, and our search suggests that further work is necessary to confirm our suspicions.
32497257 Our attention has been focused on the role of ACE2 in that its blockade by the virus increases Bradykinin and its metabolites, well known to facilitate inflammation in the lung (responsible for cough and fever), facilitate both the coagulation and complement system, three mechanisms that are typical of angioedema, cardiovascular dysfunction and sepsis, pathologies which symptoms occur in COVID-19 patients. […] Thus, we propose to pharmacologically block the kallikrein-kinin system upstream bradykinin and the ensuing inflammation, coagulation and complement activation by means of lanadelumab, which is a clinically approved drug for hereditary angioedema.
32504925 ACE2 exerts a chief role in the renin-angiotensin system (RAS) by converting angiotensin II to angiotensin-(1-7) that activates Mas receptor, inhibits ACE1, and modulates bradykinin (BK) receptor sensitivity, especially the BK type 2 receptor (BKB2R). […] ACE2 also hydrolizes des-Arg9-bradykinin (DABK), an active BK metabolite, agonist at BK type 1 receptors (BKB1R), which is upregulated by inflammation.
32534506 Nevertheless, we hypothesized that a back load build up effect on Ang II may usurp the ACE capacity and subsequently leave the bradykinin system unabated. […] Thereby, we speculated that inhibition of bradykinin synthesis and/or blockade of bradykinin B2 receptor using Aprotinin/ecallantide and Icatibant, respectively, may hold therapeutic promise in severe cases and these molecules can be advanced to clinical trials.
32544563 The virus-mediated down-regulation of ACE2 causes a burst of inflammatory cytokine release through dysregulation of the renin-angiotensin-aldosterone system (ACE/angiotensin II/AT1R axis), attenuation of Mas receptor (ACE2/MasR axis), increased activation of [des-Arg9]-bradykinin (ACE2/bradykinin B1R/DABK axis), and activation of the complement system including C5a and C5b-9 components.
32633718 Bradykinin is a potent part of the vasopressor system that induces hypotension and vasodilation and is degraded by ACE and enhanced by the angiotensin1-9 produced by ACE2. […] Comparison with BALF from controls identifies a critical imbalance in RAS represented by decreased expression of ACE in combination with increases in ACE2, renin, angiotensin, key RAS receptors, kinogen and many kallikrein enzymes that activate it, and both bradykinin receptors. […] This very atypical pattern of the RAS is predicted to elevate bradykinin levels in multiple tissues and systems that will likely cause increases in vascular dilation, vascular permeability and hypotension. […] These bradykinin-driven outcomes explain many of the symptoms being observed in COVID-19.
32653530 In this brief review, we discuss the effect of ACE inhibitor-induced bradykinin on the cardiovascular system, on the renin-angiotensin-aldosterone system (RAAS) regulation in COVID-19 patients, and analyze recent clinical studies regarding patients treated with RAAS inhibitors.
32761647 SARS-COV-2-induced ACE2 inhibition leads to the augmentation of bradykinin 1-receptor effects, as ACE2 inactivates des-Arg9-bradykinin, a bradykinin metabolite. […] SARS-COV-2 also decreases bradykinin 2-receptor effects as it affects bradykinin synthesis by inhibiting cathepsin L, a kininogenase present at the site of infection and involved in bradykinin production. […] Interestingly, the snake-derived bradykinin-potentiating peptide (BPP-10c) acts on both systems. […] BPP-10c strongly decreases angiotensin II by inhibiting ACE, increasing bradykinin-related effects on the bradykinin 2-receptor and increasing nitric oxide-mediated effects.
32769760 Furthermore, other pathways may also play important roles in COVID-19 transmission and pathogenesis; spike (S) protein proteases facilitate viral transmission by cleaving S protein that promotes viral entry into the host; neprilysin (NEP), a neutral endopeptidase known to cleave natriuretic peptides, degrades Ang I into Ang 1-7; NEP can also catabolize bradykinin and thus mitigate bradykinin’s role in inflammation, whereas, in the same context, specific bradykinin inhibitors may also negate bradykinin’s harmful effects. […] Based on these intricate mechanisms, various preventive and therapeutic strategies may be devised, such as upregulating ACE2 and/or using recombinant ACE2, and exploiting the NEP, bradykinin and serine protease pathways, in addition to anti-inflammatory and antiviral therapies.
32834893 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent for COVID-19, enters host cells via angiotensin-converting enzyme 2 (ACE2) and depletes ACE2, which is necessary for bradykinin metabolism. […] The depletion of ACE2 results in the accumulation of des-Arg (9)-bradykinin and possible bradykinin, both of which bind to bradykinin receptors and induce vasodilation, lung injury, and inflammation. […] It is well known that an overactivated contact system and excessive production of bradykinin comprise the key mechanisms that drive the pathogenesis of hereditary angioedema (HAE).
32849666 Activation of kallikrein by activated FXII leads to production of bradykinin (BK) from HK.
32967280 Increasing evidence suggests that the inflammatory response observed in covid-19 patients is initiated by the action of kinins on the bradykinin receptors. […] Accordingly, the use of bradykinin antagonists should be considered as a strategy for therapeutic intervention against covid-19 illness progression. […] Presently, icatibant is the only bradykinin antagonist drug approved. […] In the present report, we investigated the molecular features characterizing non-selective antagonists targeting the bradykinin receptors and carried out a in silico screening of approved drugs, aimed at the identification of compounds with a non-selective bradykinin antagonist profile that can be evaluated for drug repurposing. […] The study permitted to identify eight compounds as prospective non-selective antagonists of the bradykinin receptors, including raloxifene; sildenafil; cefepime; cefpirome; imatinib; ponatinib; abemaciclib and entrectinib.
32968645 Imbalance in the ACE2-RAAS- bradykinin axis and the cytokine storm could be an important mechanism leading to pathophysiological changes in pulmonary vascular and secondary refractory hypoxemia.
32990314 Angiotensin-converting enzyme (ACE) is a zinc membrane metallopeptidase that plays a key role in regulating vasoactive peptide levels and hence cardiovascular activity through its conversion of angiotensin I (Ang I) to Ang II and its metabolism of bradykinin. […] Unlike ACE, ACE2 does not metabolise bradykinin nor is it inhibited by classical ACE inhibitors.
32992731 Here, we show that the expression levels of ACE2, TMPRSS2 and other viral entry-related genes, as well as potential downstream effector genes such as bradykinin receptors, are modulated in the target organs of select disease states.
33082849 ACE-2 downregulation causes bradykinin accumulation which may exert its proliferative action via mitogen activated protein kinase pathways which has established roles in cancers of breast and kidney.
33122196 Surprisingly, SARS-CoV-2 trimeric spike protein increased ACE2 proteolytic activity ∼3-10 fold against model peptide substrates, such as caspase-1 substrate and Bradykinin-analog.
33126657 -bradykinin (DABK), are necessary for an effective defense.
33133525 It has several molecular mechanisms including antioxidant, antiapoptotic, and antifibrotic properties with inhibitory effects on Toll-like receptors, NF-κB, inflammatory cytokines and chemokines, and bradykinin.
33157320 However, eNOS derived NO occurs at low levels, unless it is during inflammation and co-stimulated by bradykinin. […] Regrettably, the bradykinin-induced vasodilation also progressively declines with age, thereby decreasing anti-viral NO production as well. […] These changes with age, low bradykinin and NO, may be the fundamental reasons that intracellular innate immunity declines with age leading to more severe COVID-19 complications.
33167852 We propose that SARS-CoV-2 activates the innate immune system through the renin-angiotensin and kallikrein-bradykinin pathways, blocks interferon production and reduces an effective adaptive immune response.
33170317 Indeed, although mostly neglected, ACE2 can also act on [des-Arg 937]-bradykinin of the kinin-kallikrein system regulating coagulation and inflammation.
33177594 Here we assembled a healthy human lung cell atlas meta-analysis with ~ 130,000 public single-cell transcriptomes and show that key elements of the bradykinin, angiotensin and coagulation systems are co-expressed with ACE2 in alveolar cells and associated with their differentiation dynamics, which could explain how changes in ACE2 promoted by SARS-CoV-2 cell entry result in the development of the three most severe clinical components of COVID-19.
33203141 NEP is implicated in the degradation of natriuretic peptides, bradykinin, substance P, adrenomedullin, and apelin that account for prevention of organ injury.
33239231 AAT inhibition of ADAM17 also prevents shedding of ACE2 and hence may preserve ACE2 inhibition of bradykinin, reducing the ability of bradykinin to cause a capillary leak in COVID-19.
33254484 Here we want to emphasize on an important post-receptor mechanism of bradykinin that is Nitric Oxide. […] This medication may abort effects of Bradykinin by inhibition of Nitric Oxide synthase inhibitor and promote oxygen saturation while it is inexpensive and ubiquitously accessible.
33298149 We hypothesize a crucial pathophysiological role for the contact pathway of coagulation and the kallikrein-bradykinin pathway.
33310922 Bradykinin was implicated in a new complex model of pathomechanism leading to the symptoms of COVID-19 created by a computer-assisted association analysis. […] According to this model, the decrease in angiotensin-converting enzyme expression leads to impaired bradykinin elimination and subsequent enrichment in the lungs. […] However, there is no mentioning of the importance of blood coagulation factor XII in increased bradykinin production, in spite of its age-dependent activation and the lower level of C1-esterase inhibitor (C1INH). […] Activated factor XII may be an important contributor to the “bradykinin storm” in elder cardiovascular patients. […] 1) Activation of the coagulation factor XII on the surface of SARS-CoV-2 infected endothelial cells may trigger the prekallikrein/kallikrein/kinin system producing bradykinin. […] Recently, beneficial results have already been observed by the clinical applications of recombinant C1INH and bradykinin receptor antagonists.
33342421 ACE-2 upregulation will ensure less formation of angiotensin II, vasodilatory effects due to the formation of angiotensin (1-7), increased breakdown of bradykinin at lung level.
33383825 Recently, it was suggested that a dysregulated bradykinin signaling can trigger the cytokine storm observed in patients with severe Covid-19. […] In the scope of a drug repurposing campaign undertaken to identify bradykinin antagonists, raloxifene was identified as prospective compound in a virtual screening process. […] The pharmacodynamics profile of raloxifene towards bradykinin receptors is reported in the present work, showing a weak selective partial agonist profile at the B2 receptor.
33404363 The kalikrein-bradykinin (BK) system and chymase are intensively interwoven with RAAS through many pathways with complex reciprocal interactions.
33461019 Outside the RAS, ACE2 hydrolyzes key peptides, such as amyloid-β, apelin, and [des-Arg9]-bradykinin.
33472675 The putative viral-induced inhibition of ACE2 could result in the defective degradation of bradykinin, a potent inflammatory substance. […] We hypothesize that increased bradykinin in the lungs is an important mechanism driving the development of pneumonia and respiratory failure in COVID-19. […] Accumulation of bradykinin in the lungs is a common side effect of ACE inhibitors leading to cough. […] In animal models, the inactivation of ACE2 leads to severe acute pneumonitis in response to lipopolysaccharide (LPS), and the inhibition of bradykinin almost completely restores the lung structure. […] We believe that inhibition of bradykinin in severe COVID-19 patients could reduce the lung inflammatory response, impacting positively on the severity of disease and mortality rates.
33552069 Previously proposed cytokine/bradykinin storm mechanisms are not incompatible with this new proposal.
33575962 Considering the modulation of neutrophil recruitment of extreme relevance for respiratory distress and lung failure prevention, we propose that P2Y14 receptor inhibition by its selective antagonist PPTN could limit neutrophil recruitment and NETosis, hence limiting excessive formation of oxygen reactive species and proteolytic activation of the kallikrein-kinin system and subsequent bradykinin storm in the alveolar septa of COVID-19 patients.