Portal hypertensive response to kinin

Kouyoumdjian, Maria; Nagaoka, Márcia Regina; Loureiro-Silva, Maurício R.; Borges, Durval Rosa

doi:10.1590/s0001-37652009000300008

Cited by 5 publications

(4 citation statements)

References 69 publications

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“…Similar protective effects were observed in cardiac, renal and liver damage models [36]. For instance, B2 activation induces a hypertensive hepatic response [37], which could play a role in malaria liver stage physiology, with modulation of hepatic blood flow and parasite distribution in the tissue.…”

Section: Discussionmentioning

confidence: 61%

Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins

Bagnaresi

Barros

Assis

et al. 2012

Malar J

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BackgroundThe malaria burden remains a major public health concern, especially in sub-Saharan Africa. The complex biology of Plasmodium, the apicomplexan parasite responsible for this disease, challenges efforts to develop new strategies to control the disease. Proteolysis is a fundamental process in the metabolism of malaria parasites, but roles for proteases in generating vasoactive peptides have not previously been explored.ResultsIn the present work, it was demonstrated by mass spectrometry analysis that Plasmodium parasites (Plasmodium chabaudi and Plasmodium falciparum) internalize and process plasma kininogen, thereby releasing vasoactive kinins (Lys-BK, BK and des-Arg9-BK) that may mediate haemodynamic alterations during acute malaria. In addition, it was demonstrated that the P. falciparum cysteine proteases falcipain-2 and falcipain-3 generated kinins after incubation with human kininogen, suggesting that these enzymes have an important role in this process. The biologic activity of peptides released by Plasmodium parasites was observed by measuring ileum contraction and activation of kinin receptors (B1 and B2) in HUVEC cells; the peptides elicited an increase in intracellular calcium, measured by Fluo-3 AM fluorescence. This effect was suppressed by the specific receptor antagonists Des-Arg9[Leu8]-BK and HOE-140.ConclusionsIn previously undescribed means of modulating host physiology, it was demonstrated that malaria parasites can generate active kinins by proteolysis of plasma kininogen.

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Section: Discussionmentioning

confidence: 61%

Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins

Bagnaresi

Barros

Assis

et al. 2012

Malar J

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“…Kinin B1R is an important inflammatory mediator and is correlated to the hemodynamic response to kinins, with increased blood pressure induced by des-Arg 9 -bradykinin [42, 43]. In hepatic perfusion, BK induces a portal hypertensive response that is mediated by B2R and modulated by NO system in healthy liver, as well as, in inflammatory, fibrotic, and cirrhotic conditions [28]. The B1R and B2R antagonists promote downregulation of pro-inflammatory molecules and upregulation of anti-inflammatory molecules, representing a new therapeutic strategy for the prevention and treatment of renal ischemia-warm reperfusion injury [44].…”

Section: Discussionmentioning

confidence: 99%

“…The hepatic microcirculation can be modulated by the kinin-signalling pathway through activation of B1 or B2 kinin receptors resulting in a portal hypertensive response [28]. Both receptors are coupled to G protein, but the B2R is constitutively expressed, whereas the B1R expression is inducible by inflammatory cytokines in different tissues such as smooth muscle cells, endothelial cells, human sinusoidal cells from fibrotic liver and others [27, 29, 30].…”

Section: Introductionmentioning

confidence: 99%

Malaria infection promotes a selective expression of kinin receptors in murine liver

Ventura

Carvalho

Barros

et al. 2019

Malar J

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Background Malaria represents a worldwide medical emergency affecting mainly poor areas. Plasmodium parasites during blood stages can release kinins to the extracellular space after internalization of host kininogen inside erythrocytes and these released peptides could represent an important mechanism in liver pathophysiology by activation of calcium signaling pathway in endothelial cells of vertebrate host. Receptors (B1 and B2) activated by kinins peptides are important elements for the control of haemodynamics in liver and its physiology. The aim of this study was to identify changes in the liver host responses (i.e. kinin receptors expression and localization) and the effect of ACE inhibition during malaria infection using a murine model. Methods Balb/C mice infected by Plasmodium chabaudi were treated with captopril, an angiotensin I-converting enzyme (ACE) inhibitor, used alone or in association with the anti-malarial chloroquine in order to study the effect of ACE inhibition on mice survival and the activation of liver responses involving B1R and B2R signaling pathways. The kinin receptors (B1R and B2R) expression and localization was analysed in liver by western blotting and immunolocalization in different conditions. Results It was verified that captopril treatment caused host death during the peak of malaria infection (parasitaemia about 45%). B1R expression was stimulated in endothelial cells of sinusoids and other blood vessels of mice liver infected by P. chabaudi . At the same time, it was also demonstrated that B1R knockout mice infected presented a significant reduction of survival. However, the infection did not alter the B2R levels and localization in liver blood vessels. Conclusions Thus, it was observed through in vivo studies that the vasodilation induced by plasma ACE inhibition increases mice mortality during P. chabaudi infection. Besides, it was also seen that the anti-malarial chloroquine causes changes in B1R expression in liver, even after days of parasite clearance. The differential expression of B1R and B2R in liver during malaria infection may have an important role in the disease pathophysiology and represents an issue for clinical treatments.

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“…However, studies have indicated that action of bradykinin is not limited to these receptors, so possible anti-inflammatory effects of carboxypeptidase inhibition are controversial and should be tested separately. 44 …”

Section: Introductionmentioning

confidence: 99%

Medicinal leech therapy—an overall perspective

Sığ

Güney

Güçlü

et al. 2017

Integrative Medicine Research

105

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Complementary medicine methods have a long history, but modern medicine has just recently focused on their possible modes of action. Medicinal leech therapy (MLT) or hirudotherapy, an old technique, has been studied by many researchers for possible effects on various diseases such as inflammatory diseases, osteoarthritis, and after different surgeries. Hirudo medicinalis has widest therapeutic usage among the leeches, but worldwide, many different species were tested and studied. Leeches secrete more than 20 identified bioactive substances such as antistasin, eglins, guamerin, hirudin, saratin, bdellins, complement, and carboxypeptidase inhibitors. They have analgesic, anti-inflammatory, platelet inhibitory, anticoagulant, and thrombin regulatory functions, as well as extracellular matrix degradative and antimicrobial effects, but with further studies, the spectrum of effects may widen. The technique is cheap, effective, easy to apply, and its modes of action have been elucidated for certain diseases. In conclusion, for treatment of some diseases, MLT is not an alternative, but is a complementary and/or integrative choice. MLT is a part of multidisciplinary treatments, and secretes various bioactive substances. These substances vary among species and different species should be evaluated for both treatment capability and their particular secreted molecules. There is huge potential for novel substances and these could be future therapeutics.

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Portal hypertensive response to kinin

Cited by 5 publications

References 69 publications

Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins

Intracellular proteolysis of kininogen by malaria parasites promotes release of active kinins

Malaria infection promotes a selective expression of kinin receptors in murine liver

Medicinal leech therapy—an overall perspective

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