Role of Bradykinin B2 and B1 Receptors in the Local, Remote, and Systemic Inflammatory Responses That Follow Intestinal Ischemia and Reperfusion Injury

Souza, Danielle G.; Lomez, Eliane S. L.; Pinho, Vanessa; Pesquero, João Bosco; Bäder, Michael; Pesquero, Jorge L.; Teixeira, Mauro Martins

doi:10.4049/jimmunol.172.4.2542

Cited by 81 publications

(69 citation statements)

References 41 publications

(45 reference statements)

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“…Neutrophil migration in inflamed tissues is reduced in kinin B1 knockout mice, indicating that the pro-inflammatory effect of kinin is mediated by the B1 receptor [33]. Furthermore, the inflammatory response after ischemia/reperfusion injury is significantly reduced in B1 receptor-deficient mice, and pretreatment with icatibant reverses this antiinflammatory effect [34]. These combined results suggest that the B1 receptor is proinflammatory whereas the B2 receptor protects against tissue injury.…”

Section: Discussionmentioning

confidence: 94%

Tissue kallikrein infusion prevents cardiomyocyte apoptosis, inflammation and ventricular remodeling after myocardial infarction

Yao

Yin

Shen

et al. 2007

Regulatory Peptides

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We investigated the effect of tissue kallikrein infusion on cardiac protection at acute and sub-acute phases after myocardial infarction (MI). Immediately after MI, rats were infused with purified tissue kallikrein, with or without icatibant (a kinin B2 receptor antagonist). Intramyocardial injection of kallikrein reduced myocardial infarct size and inhibited cardiomyocyte apoptosis at 1 day after MI associated with increased nitric oxide levels, Akt and glycogen synthase kinase-3β phosphorylation and decreased caspase-3 activation. Kallikrein infusion for 7 days improved cardiac function, normalized left ventricular wall thickness and decreased monocyte/macrophage infiltration in the infarct heart. Kallikrein treatment reduced NADH oxidase expression and activity, superoxide formation and malondialdehyde levels, and reduced MAPK and Iκ-Bα phosphorylation, NF-κB activation and MCP-1 and VCAM-1 expression. Kallikrein's effects were all blocked by icatibant. These results indicate that kallikrein through kinin B2 receptor activation prevents apoptosis, inflammation and ventricular remodeling by increased nitric oxide formation and suppression of oxidative stress-mediated signaling pathways.

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Section: Discussionmentioning

confidence: 94%

Tissue kallikrein infusion prevents cardiomyocyte apoptosis, inflammation and ventricular remodeling after myocardial infarction

Yao

Yin

Shen

et al. 2007

Regulatory Peptides

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“…In contrast to the consensus that ACEIs have beneficial effects on I/R injury, previous reports are conflicting with respect to the effects of pharmacological agents interacting with the bradykinin receptors (20)(21)(22). In addition, several studies have suggested that agonism of the B1R and B2R may have different effects on the severity of I/R injury (21)(22)(23).…”

Section: Discussionmentioning

confidence: 95%

“…In addition, several studies have suggested that agonism of the B1R and B2R may have different effects on the severity of I/R injury (21)(22)(23). In contrast, lack of the B1R (42) or B2R (43) aggravates the I/R injury in the heart and brain of mice, whereas adenovirus-mediated gene transfer of tissue kallikrein protects against ischemic stroke in rats (44).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to the consensus that ACEIs have beneficial effects on I/R injury, previous studies have produced conflicting results concerning the effect on I/R injury in different organs of stimulating the two bradykinin receptors, B1R and B2R (20)(21)(22). In addition, several studies have suggested that agonism of the B1R may have opposite effects from agonism of the B2R on the severity of I/R injury (23).…”

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confidence: 97%

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Bradykinin B1 and B2 receptors both have protective roles in renal ischemia/reperfusion injury

Kakoki

McGarrah

Kim

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

117

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To explore the role of the kallikrein-kinin system in relation to ischemia/reperfusion injury in the kidney, we generated mice lacking both the bradykinin B1 and B2 receptor genes (B1RB2R-null, Bdkrb1 ؊/ ؊/Bdkrb2 ؊/؊ ) by deleting the genomic region encoding the two receptors. In 4-month-old mice, blood pressures were not significantly different among B1RB2R-null, B2R-null (Bdkrb2 ؊/؊ ), and WT mice. After 30 min of bilateral renal artery occlusion and 24 h of reperfusion, mortality rates, renal histological and functional changes, 8-hydroxy-2 -deoxyguanosine levels in total DNA, mtDNA deletions, and the number of TUNEL-positive cells in the kidneys increased progressively in the following order (from lowest to highest): WT, B2R-null, and B1RB2R-null mice. Increases in mRNA levels of TGF-␤1, connective tissue growth factor, and endothelin-1 after ischemia/reperfusion injury were also exaggerated in the same order (from lowest to highest): WT, B2R-null, and B1RB2R-null. Thus, both the B1 and B2 bradykinin receptors play an important role in reducing DNA damage, apoptosis, morphological and functional kidney changes, and mortality during renal ischemia/reperfusion injury.hypoxia ͉ mitochondria ͉ oxidative stress I schemic tissue injuries, including stroke, myocardial infarction, and ischemic acute renal failure, are devastating complications in patients with hypertension, diabetes, atherosclerosis, and senescence. In organ transplantation, damage to allografts during any ischemic period before the transplant markedly influences short-term and long-term graft function and outcome (1). Furthermore, although reoxygenation after ischemia is essential for cell survival, damage also develops during the reperfusion period. Previous studies have shown that acute ATP depletion, intracellular Ca 2ϩ accumulation, and increased generation of reactive oxygen species by mitochondria all play important roles in the pathogenesis of ischemia/reperfusion (I/R) injury (2).Angiotensin-I-converting enzyme (ACE) inhibitors (ACEIs) reduce not only chronic cardiovascular remodeling after ischemia but also acute tissue injury caused by I/R in the heart (3), lung (4), liver (5), and kidneys (6, 7). Several observations indicate that the beneficial effects of ACEIs in the acute phase are mainly due to activation of the bradykinin nitric oxide (NO) cascade as a result of inhibition of the inactivation of bradykinin, rather than due to suppression of angiotensin II formation. Thus, ACEIs are much more effective than angiotensin type I receptor antagonists in protecting against I/R (8-10), and bradykinin B2 receptor (B2R) antagonists and NO synthase blockers markedly attenuate the protective effects of ACEIs (8, 9, 11).Bradykinin and lysyl-bradykinin (kallidin) are generated from kininogens by the kallikreins and some other serine proteases. ACE, which is a carboxydipeptidase, inactivates both peptides by removing two amino acids from their carboxyl termini. In mammals, at least two receptors have been identified: the bradykinin B1 receptor (B...

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“…The B 1 receptor is the key towards initiating inflammatory responses; injection of carrageenan into ko-B 1 mice resulted in downregulation of neutrophil infiltration (23). Likewise, cytokine-mediated neutrophil infiltration of the lung is apparent in wt mice following intestinal ischaemia-reperfusion, but abrogated in ko-B 1 counterparts, demonstrating reduced inflammation in ko-B 1 animals (25). In a murine model of renal fibrosis, B 1 receptor expression was upregulated, induced by urethral obstruction.…”

Section: Physiological Responsementioning

confidence: 99%

New topics in bradykinin research

Maurer

Bäder

Baş

et al. 2011

Allergy

154

129

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The kinins are a family of vasoactive peptides including bradykinin, kallidin and methionyl-lysyl-bradykinin, the latter two compounds being converted very rapidly to bradykinin by aminopeptidases. Bradykinin is a low molecular weight (1060.21 Da; C 50 H 73 N 15 O 11 ) nonapeptide, which is rapidly metabolized by endogenous metalloproteases including angiotensin-converting enzyme (ACE or kininase II), neutral endopeptidase (NEP or neprilysin), carboxypeptidase N (CPN or kininase I) and aminopeptidase P (1). Bradykinin has only a short plasma half-life of 15 s, and circulating levels are usually relatively low (0.2-7.1 pM) (2, 3).Much progress was made in understanding the physiological role of kinins with the development of selective antagonists for endothelial B 1 and B 2 receptors (4) and of C1 esterase inhibitor (C1-INH)-and B 2 -receptor-transgenic mice (5, 6). Bradykinin binds these receptors, exerting potent effects in different pathophysiological states (7) (Fig. 1). For example, bradykinin exerts potent antihypertensive, antithrombogenic, antiproliferative and antifibrogenic effects (8) as summarised in Table 1. Bradykinin also participates in inflammatory processes by activating endothelial cells to promote vasodilation and increased vascular permeability, producing classical symptoms of inflammation such as redness, heat, swelling and pain (1, 9). Specifically, bradykinin contributes to tissue hyper-responsiveness and local inflammation in allergic rhinitis, asthma and anaphylaxis, while bradykinin-dependent angioedema can result from hereditary or acquired C1-INH deficiency or the use of ACE inhibitors (ACEi) to treat hypertension, heart failure, diabetes or scleroderma. AbstractBradykinin has been implicated to contribute to allergic inflammation and the pathogenesis of allergic conditions. It binds to endothelial B 1 and B 2 receptors and exerts potent pharmacological and physiological effects, notably, decreased blood pressure, increased vascular permeability and the promotion of classical symptoms of inflammation such as vasodilation, hyperthermia, oedema and pain. Towards potential clinical benefit, bradykinin has also been shown to exert potent antithrombogenic, antiproliferative and antifibrogenic effects. The development of pharmacologically active substances, such as bradykinin receptor blockers, opens up new therapeutic options that require further research into bradykinin. This review presents current understanding surrounding the role of bradykinin in nonallergic angioedema and other conditions seen by allergists and emergency physicians, and its potential role as a therapeutic target.

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Role of Bradykinin B2 and B1 Receptors in the Local, Remote, and Systemic Inflammatory Responses That Follow Intestinal Ischemia and Reperfusion Injury

Cited by 81 publications

References 41 publications

Tissue kallikrein infusion prevents cardiomyocyte apoptosis, inflammation and ventricular remodeling after myocardial infarction

Tissue kallikrein infusion prevents cardiomyocyte apoptosis, inflammation and ventricular remodeling after myocardial infarction

Bradykinin B1 and B2 receptors both have protective roles in renal ischemia/reperfusion injury

New topics in bradykinin research

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