BRADYKININ


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



Drug Sentece Context


Table 1. Analysis of context sentence of bradykinin gene in 24 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.