Role of endothelin during experimental <i>Trypanosoma cruzi</i> infection in rats

Camargos, Elizabeth R.S.; Machado, Conceição R. S.; Teixeira, Antônio Lúcio; Rocha, Lamara Laguardia Valente; Ferreira, Anderson J.; Almeida, Alvair P.; Barton, Matthias; Teixeira, Mauro Martins

doi:10.1042/cs103s064s

Cited by 17 publications

(12 citation statements)

References 15 publications

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“…Blood pressure and heart rate are regulated by circulating neuropeptides which involve the brain-cardiac axis (Xiang 1994, Matsumara et al 2003, Pedrazzini et al 2003 and by endogenous molecules synthesised by heart neurons (Lillywhite et al 1999). While many studies have dealt with the distribution and physiological effect of several neuropeptides on vertebrate hearts (Masini et al 1997, Wong et al 1998, Henning & Sawmiller 2001, there has been very little work on how parasites can induce alterations in the cardiac intrinsic nervous system (Camargos et al 2002, Rodrigues et al 2002. Of the records that do exist, none refer to parasitic infections in fishes.…”

Section: Resultsmentioning

confidence: 99%

Histopathology, ultrastructure and immunohistochemistry of Coregonus lavaretus hearts naturally infected with Ichthyocotylurus erraticus (Trematoda)

Dezfuli¹,

Giari²,

Simoni³

et al. 2005

Dis. Aquat. Org.

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Histopathological, ultrastructural and immunohistochemical investigations were conducted on 26 specimens of powan Coregonus lavaretus (L.) from Loch Lomond (Scotland). The hearts of all 26 powan (15 females and 11 males) investigated harboured metacercariae of the digenean trematode Ichthyocotylurus erraticus (Rudolphi, 1809). The vast majority of metacercariae were located either singly or as an aggregation of white cysts on the surface of the bulbus arteriosus. The intensity of infection ranged from 2 to 200 larvae heart -1 , although the number of metacercariae found on male powan did not exceed 13. Histochemically, the parasite cyst wall gave a strong positive reaction with periodic acid schiff (PAS) and a faint positive signal with Azan-Mallory stain. All the metacercariae cysts were embedded in a granulomatous proliferation of heart epicardium tissue, forming a reactive fibroconnective capsule around the parasite. The capsule enclosing the parasite (produced by the host's reaction to the parasite) measured 13.57 to 90.20 µm (37.43 ± 3.56) in thickness. Within the capsule wall, eosinophilic granular cells (EGCs), granulocytes, melanocytes and, in some instances, partially degenerated or vacuolated epithelioid cells were observed in close proximity to the cyst wall. Pigment-bearing macrophages were scattered throughout the granulomatous host-tissue reaction and as macrophage aggregates (MAs) within the capsules surrounding parasites. Immunohistochemical tests were applied to infected heart sections using 12 different antisera. Nerve fibres immunoreactive to bombesin, substance P (SP), and atrial natriuretic peptide (ANP) antisera were observed in close proximity to the parasite larvae. The presence of a serotonin-like substance was also observed within host immune-cells surrounding trematode cysts. Large cells of the epicardium were found to be immunoreactive to met-enkephalin and vasoactive intestinal peptide (VIP) antisera but not immunoreactive to anti-protein gene-product 9.5 (PGP9.5) sera. KEY WORDS: Trematode infection · Immunohistochemistry · Neuromodulators · Heart · Coregonus lavaretusResale or republication not permitted without written consent of the publisher

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Section: Resultsmentioning

confidence: 99%

Histopathology, ultrastructure and immunohistochemistry of Coregonus lavaretus hearts naturally infected with Ichthyocotylurus erraticus (Trematoda)

Dezfuli¹,

Giari²,

Simoni³

et al. 2005

Dis. Aquat. Org.

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“…Moreover, the compound was unable to enhance the killing mediated by a suboptimal concentration of IFN-γ (1 U/mL). For comparison, treatment with IFN-γ (100 U/mL) greatly enhanced the killing of T. cruzi by peritoneal macrophages Endothelin-1 receptor antagonist in acute T. cruzi infection www.bjournal.com.br gesting that these receptors in fact play a role in the defense against T. cruzi (14,15,17). However, we also used BSF461314, an ET A receptor antagonist, in T. cruzi-infected mice and did not find changes in parasitemia or parasitism (Roffê E, Souza ALS, Machado PP, Barcelos LS, Romanha AJ, Mariano FS, Silva JS, Machado CR, Tanowitz HB, Teixeira MM, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

“…In T. cruzi-infected mice, treatment with phosphoramidon, an endothelinconverting enzyme and neutral endopeptidase inhibitor, and verapamil, a first generation L-type calcium channel antagonist, reduced or abrogated mortality and attenuated cardiac pathology and dysfunction parameters (10)(11)(12)(13). Similarly, treatment with BSF461314, an ET A receptor antagonist, was able to prevent changes in coronary flow in T. cruzi-infected rats (14,15). In the latter studies, ET A receptor antagonist treatment was associated with enhanced parasitemia, inflammation and parasitism in myocardium and diaphragm.…”

Section: Introductionmentioning

confidence: 96%

“…An increase of myocardial parasite load and inflammation was observed also in rats treated with the ET A/B receptor antagonist bosentan (16). These findings suggest that ET-1 is part of a cascade of events leading to a protective immune response against acute T. cruzi infection in rats (14)(15)(16). However, the role of ET-1 in the ability of the host to deal with infection has not been determined in any other species.…”

Section: Introductionmentioning

confidence: 99%

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Endothelin-1 receptors play a minor role in the protection against acute Trypanosoma cruzi infection in mice

Roffê

Souza

Machado

et al. 2007

Braz J Med Biol Res

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Chagas' disease, caused by the protozoan Trypanosoma cruzi, is a major cause of cardiovascular disability in countries where it is endemic. Damage to the heart microvasculature has been proposed to be an important factor in the pathogenesis of heart dysfunction. Endothelin-1 (ET-1) is a potent vasoconstrictor and exerts its effects via specific ET A and ET B receptors. A few studies have suggested a role for ET-1 and its receptors in the pathogenesis of Chagas' disease. We investigated the effects of treatment with bosentan, an ET A /ET B receptor antagonist, on the course of T. cruzi infection (Y strain) in C57Bl/6 mice. Treatment with bosentan (100 mg kg -1 day -1 ) was given per os starting day 0 after infection until sacrifice. Bosentan significantly increased myocardial inflammation, with no effects on parasitemia. Although the total number of nests was similar, a lower number of intact amastigote nests was found in the heart of bosentan-treated animals. Bosentan failed to affect the infection-associated increase in the cardiac levels of the cytokines IFN-γ and TNF-α and the chemokines CCL2/MCP-1, CCL3/MIP-1α and CCL5/RANTES. In vitro, pre-incubation with ET-1 (0.1 µM) 4 h before infection enhanced the uptake of the parasites by peritoneal macrophages, and this effect was abrogated when macrophages were pre-treated with bosentan (1 µM) 15 min before incubation with ET-1. However, ET-1 did not alter killing of intracellular parasites after 48 h of in vitro infection. Our data suggest that bosentan-treated mice have a delay in controlling parasitism which is compensated for exacerbated inflammation. Infection is eventually controlled in these animals and lethality is unchanged, demonstrating that ET-1 plays a minor role in the protection against acute murine T. cruzi infection.

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“…During the course of the Chagas disease infection, parasites have been observed in the microvascular endothelia of the aorta and coronary arteries before detection of the parasitemia 10,16,17 . Cultures of endothelial cells infected with T. cruzi show complex alterations in mechanisms that are critical to maintain normal vascular function [18][19][20] .…”

Section: Methodsmentioning

confidence: 99%

Disfunção endotelial venosa em pacientes com doença de Chagas sem insuficiência cardíaca

Plentz¹,

Irigoyen²,

Müller³

et al. 2006

Arq. Bras. Cardiol.

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Original Article M a i l i n g A d d r e s s : R o d r i g o D el l a M e á P l e n t z • R u a J o ã o M a n o e l , 1 3 5 2 -9 8 1 0 -5 1 7 0 -C r u z A l t a , R S -B r a z i l E-mail: roplentz@yahoo.com. OBJECTIVETo analyze the venous endothelial function in Chagas' disease patients without heart failure. METHODSThe Chagas' disease Group (G1) was composed by 14 women and 2 men aged 46 ± 2,7 and the Control Group (G0) by 7 women and 1 man matched by age, weight and height. Dorsal Hand Vein Compliance Technique was used to evaluate the venous endothelial function. Crescent doses of phenylephrine were infused to get a 70% preconstriction of the vein; after that, acetylcholine and sodium nitroprusside were respectively administrated to analyze the endothelium-dependent and -independent venodilation. RESULTSNo significant systemic hemodynamic changes were observed in both groups during the experiment. The necessary phenylephrine dose to reach 70% preconstriction of the vein was signifi cantly higher in the G1 (1116 ± 668,2 ng/ml) compared to G0 (103 ± 28 ng/ml) p = 0,05. The endothelium-dependent venous dilation was signifi cantly lower in G1 (65,5 ± 8%) compared to G0 (137 ± 20 %) p = 0,009. No difference was observed in the endothelium-independent venous dilatation between groups.

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Role of endothelin during experimental Trypanosoma cruzi infection in rats

Cited by 17 publications

References 15 publications

Histopathology, ultrastructure and immunohistochemistry of Coregonus lavaretus hearts naturally infected with Ichthyocotylurus erraticus (Trematoda)

Histopathology, ultrastructure and immunohistochemistry of Coregonus lavaretus hearts naturally infected with Ichthyocotylurus erraticus (Trematoda)

Endothelin-1 receptors play a minor role in the protection against acute Trypanosoma cruzi infection in mice

Disfunção endotelial venosa em pacientes com doença de Chagas sem insuficiência cardíaca

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