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Renin angiotensin system molecules and nitric oxide local interactions in the adrenal gland of Trypanosoma cruzi infected rats

  • Immunology and Host-Parasite Interactions - Short Communication
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Abstract

Chagas disease (CD) is a tropical zoonosis caused by the protozoan Trypanosoma cruzi. Severe autonomic dysfunction like reduced cardiac catecholamine-containing or acetylcholinesterase-positive innervation have been reported in CD. Renin-angiotensin system (RAS) seems to participate in the regulation of adrenal catecholamine secretion by adrenal medullary chromaffin cells, which might be dependent of nitric oxide (NO) pathways. To investigate the levels of RAS components in the adrenal gland during the acute infection with Y strain T. cruzi and in response to acute administration of an inhibitor of the enzyme NO synthase, L-NAME. Male Holtzman rats were inoculated intraperitoneally with Y strain T. cruzi and received L-NAME or tap water from one day before the infection until 13 or 17 days post-inoculation (dpi). The concentration of RAS molecules in the adrenal tissue was evaluated by ELISA immunoassay. Angiotensin converting enzyme 1 (ACE1) levels were significantly lower at 17 dpi when compared to 13 dpi. No significant differences were found compared with baseline, and no changes were detected in adrenal tissue levels of angiotensin converting enzyme 2 (ACE2), angiotensin II, or angiotensin-(1-7). Moreover, the treatment with L-NAME did not influence the levels of RAS components in adrenal tissue during the course of T. cruzi infection. We provided the first evidence that levels of RAS molecules change in the adrenal gland during acute phase of T. cruzi infection. Future studies are necessary to fully address the role of NO in RAS-associated adrenal gland function in CD.

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References

  • Abwainy A, Babiker F, Akhtar S, Benter IF (2016) Endogenous angiotensin-(1-7)/Mas receptor/NO pathway mediates the cardioprotective effects of pacing postconditioning. Am J Physiol Heart Circ Physiol 310:104–112

    Article  Google Scholar 

  • Barbosa AA Jr, Andrade ZA (1984) Identificação do Trypanosoma cruzi nos tecidos extracardíacos de portadores de miocardite crônica chagásica. Rev Soc Bras Med Trop 17:123–126

    Article  Google Scholar 

  • Belloni AS, Andreis PG, Macchi V, Gottardo G, Malendowicz LK, Nussdorfer GG (1998) Distribution and functional significance of angiotensin-II AT1- and AT2-receptor subtypes in the rat adrenal gland. Endocr Res 24:1–15

    Article  CAS  Google Scholar 

  • Bern C (2015) Chagas' Disease. N Engl J Med 373:456–466

    Article  CAS  Google Scholar 

  • Boehm M, Nabel EG (2002) Angiotensin-converting enzyme 2--a new cardiac regulator. N Engl J Med 347:1795–1797

    Article  Google Scholar 

  • Bucher M, Hobbhahn J, Kurtz A (2001a) Nitric oxide-dependent down-regulation of angiotensin II type 2 receptors during experimental sepsis. Crit Care Med 29:1750–1755

    Article  CAS  Google Scholar 

  • Bucher M, Ittner KP, Hobbhahn J, Taeger K, Kurtz A (2001b) Downregulation of angiotensin II type 1 receptors during sepsis. Hypertension 38:177–182

    Article  CAS  Google Scholar 

  • Carey RM, Siragy HM (2003) Newly recognized components of the renin-angiotensin system: potential roles in cardiovascular and renal regulation. Endocr Rev 24:261–271

    Article  CAS  Google Scholar 

  • Chagas C (1916) Tripanosomiase americana: forma aguda da molestia. Mem Inst Oswaldo Cruz 8:37–60

    Article  Google Scholar 

  • Correa-de-Santana E et al (2006) Hypothalamus-pituitary-adrenal axis during Trypanosoma cruzi acute infection in mice. J Neuroimmunol 173:12–22

    Article  CAS  Google Scholar 

  • Crackower MA, Sarao R, Oudit GY, Yagil C, Kozieradzki I, Scanga SE, Oliveira-dos-Santos A, da Costa J, Zhang L, Pei Y, Scholey J, Ferrario CM, Manoukian AS, Chappell MC, Backx PH, Yagil Y, Penninger JM (2002) Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 417:822–828

    Article  CAS  Google Scholar 

  • Donoghue M et al (2000) A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res 87:1–9

    Article  Google Scholar 

  • Ferrario CM, Varagic J (2010) The ANG-(1-7)/ACE2/mas axis in the regulation of nephron function. Am J Physiol Ren Physiol 298:1297–1305

    Article  Google Scholar 

  • Fyhrquist F, Saijonmaa O (2008) Renin-angiotensin system revisited. J Intern Med 264:224–236

    Article  CAS  Google Scholar 

  • Haspula D, Clark MA (2018) Molecular basis of the brain renin angiotensin system in cardiovascular and neurologic disorders: uncovering a key role for the astroglial angiotensin type 1 receptor AT1R. J Pharmacol Exp Ther 366:251–264

    Article  CAS  Google Scholar 

  • Machado CRS, Ribeiro ALP (1989) Experimental american trypanomiasis in rats: sympathetic denervation, parasitism and inflammatory process. Mem Inst Oswaldo Cruz 84:549–556

    Article  CAS  Google Scholar 

  • Machado AB, Machado CR, Gomez MV (1979) Trypanosoma cruzi: acetylcholine content and cholinergic innervation of the heart in rats. Exp Parasitol 47:107–115

    Article  CAS  Google Scholar 

  • Machado CR, Gomez MV, Machado AB (1987) Changes in choline acetyltransferase activity of rat tissues during Chagas’ disease. Braz J Med Biol Res 20:697–702

    CAS  PubMed  Google Scholar 

  • Machado CRS, de Oliveira DA, Magalhaes MJ, EMRD C, Ramalho-Pinto FJ (1994) Trypanosoma cruzi infection in rats induced early lesion of the heart noradrenergic nerve terminals by a complement-independent mechanism. J Neural Transm / General Section 97:149–159

    Article  CAS  Google Scholar 

  • Machado CR, Camargos ER, Guerra LB, Moreira MC (2000) Cardiac autonomic denervation in congestive heart failure: comparison of Chagas’ heart disease with other dilated cardiomyopathy. Hum Pathol 31:3–10

    Article  CAS  Google Scholar 

  • Martineau D, Lamouche S, Briand R, Yamaguchi N (1999) Functional involvement of angiotensin AT2 receptor in adrenal catecholamine secretion in vivo. Can J Physiol Pharmacol 77:367–374

    Article  CAS  Google Scholar 

  • Mazzocchi G, Gottardo G, Macchi V, Malendowicz LK, Nussdorfer GG (1998) The AT2 receptor-mediated stimulation of adrenal catecholamine release may potentiate the AT1 receptor-mediated aldosterone secretagogue action of angiotensin-II in rats. Endocr Res 24:17–28

    Article  CAS  Google Scholar 

  • Miranda AS, Rachid MA, Souza CF, Oliveira BDS, Ferreira RN, Martinelli PM, Teixeira AL, Camargos ERS, Simões E Silva AC (2019) Interactions between local renin angiotensin system and nitric oxide in the brain of Trypanosoma cruzi infected rats. Acta Trop 194:36–40

    Article  CAS  Google Scholar 

  • Paul M, Poyan Mehr A, Kreutz R (2006) Physiology of local renin-angiotensin systems. Physiol Rev 86:747–803

    Article  CAS  Google Scholar 

  • Perez-Molina JA, Molina I (2018) Chagas disease. Lancet 391:82–94

    Article  Google Scholar 

  • Petray P, Rottenberg ME, Grinstein S, Orn A (1994) Release of nitric oxide during the experimental infection with Trypanosoma cruzi. Parasite Immunol 16:193–199

    Article  CAS  Google Scholar 

  • Rachid MA et al (2019) Effect of blockade of nitric oxide in heart tissue levels of Renin Angiotensin System components in acute experimental Chagas disease. Life Sci 219:336–342

    Article  CAS  Google Scholar 

  • Rassi A Jr, Rassi A, Marin-Neto JA (2010) Chagas disease. Lancet 375:1388–1402

    Article  Google Scholar 

  • Santos RA, Ferreira AJ (2007) Angiotensin-(1-7) and the renin-angiotensin system. Curr Opin Nephrol Hypertens 16:122–128

    Article  CAS  Google Scholar 

  • Santos RA, Simoes e Silva AC, Maric C, Silva DM, Machado RP, de Buhr I, Heringer-Walther S, Pinheiro SV, Lopes MT, Bader M, Mendes EP, Lemos VS, Campagnole-Santos MJ, Schultheiss HP, Speth R, Walther T (2003) Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci U S A 100:8258–8263

    Article  CAS  Google Scholar 

  • Schaller MD, Waeber B, Nussberger J, Brunner HR (1985) Angiotensin II, vasopressin, and sympathetic activity in conscious rats with endotoxemia. Am J Phys 249:1086–1092

    Google Scholar 

  • Teixeira AL Jr et al (2001) Cardiac autonomic denervation and functional response to neurotoxins during acute experimental Chagas’ disease in rats. Auton Neurosci 89:128–132

    Article  CAS  Google Scholar 

  • Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ (2000) A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem 275:33238–33243

    Article  CAS  Google Scholar 

  • WHO (2018) MCEE-WHO methods and data sources for child causes of death 2000-2017. https://wwwwhoint/healthinfo/global_burden_disease/childcod_methods_2000_2017pdf?ua=1 Accessed March 10, 2018

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Data availability statement

All the data used to support the findings of this study are available from the corresponding author upon request.

Funding

This work was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG). MAR, ALT, and ACSS are ‘CNPq Productivity Fellowship’ recipients. ASM is a 2016 NARSAD Young Investigator Grant Awardee from the Brain and Behavior Research Foundation.

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Authors and Affiliations

  1. Departamento de Morfologia, Instituto de Ciências Biológicas, UFMG, Belo Horizonte, Minas Gerais, Brazil

    Aline Silva Miranda, Elizabeth R. S. Camargos, Bruna da Silva Oliveira, Rodrigo Novaes Ferreira & Patrícia Massara Martinelli

  2. Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, UFMG, Avenida Alfredo Balena, 190, 2nd floor, room # 281, Belo Horizonte, Minas Gerais, 30130-100, Brazil

    Aline Silva Miranda, Lucas Alexandre Santos Marzano, Alessandra Cristina Santos Marzano & Ana Cristina Simões e Silva

  3. Neuropsychiatry Program, Department of Psychiatry & Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA

    Antônio Lúcio Teixeira

  4. Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil

    Milene Alvarenga Rachid

Authors
  1. Aline Silva Miranda
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  2. Elizabeth R. S. Camargos
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  3. Lucas Alexandre Santos Marzano
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  4. Alessandra Cristina Santos Marzano
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  5. Bruna da Silva Oliveira
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  6. Rodrigo Novaes Ferreira
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  7. Patrícia Massara Martinelli
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  8. Antônio Lúcio Teixeira
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  9. Milene Alvarenga Rachid
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  10. Ana Cristina Simões e Silva
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Corresponding author

Correspondence to Aline Silva Miranda.

Ethics declarations

Care and anesthesia followed the guidelines for Laboratory Animals Care established stipulated by The National Institute of Biological Sciences. The study protocol and all experimental procedures were approved by the Ethical Review Board of Federal University of Minas Gerais, Belo Horizonte, Brazil (CEUA/UFMG, Protocol number 340/2014).

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The authors declare that they have no conflict of interest.

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Section Editor: Hiroshi Sato

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Miranda, A.S., Camargos, E.R.S., Marzano, L.A.S. et al. Renin angiotensin system molecules and nitric oxide local interactions in the adrenal gland of Trypanosoma cruzi infected rats. Parasitol Res 119, 333–337 (2020). https://doi.org/10.1007/s00436-019-06485-6

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