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Anti-inflammatory action of the renin-angiotensin system in fever and hypothermia during experimental sepsis

Grant number: 20/11003-4
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2020
Effective date (End): October 31, 2021
Field of knowledge:Health Sciences - Nursing - Medical-Surgical Nursing
Principal Investigator:Evelin Capellari Cárnio
Grantee:Marco Antonio Marangão Filho
Host Institution: Escola de Enfermagem de Ribeirão Preto (EERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:16/17681-9 - Pathophysiological changes during systemic inflammation, AP.TEM


Syndromes associated with systemic inflammation (for example, sepsis and septicshock) generally have high mortality and remain a challenge in emergency medicine.Systemic inflammation is usually accompanied by changes in body temperature: fever orhypothermia. In animal studies, systemic inflammation is often modeled after the use of CecalLigation and Puncture (CLP), which consists of perforating the cecum, allowing the release offecal material in the peritoneal cavity to generate an exacerbated immune response, inducedby polymicrobial infection. Mediators of fever and hypothermia are called endogenouspyrogens and cryogenic; they are produced when the innate immune system recognizes aninfectious pathogen. In systemic inflammation, there is an exacerbated release ofinflammatory mediators, which generate vascular damage and promote hypotension,tachycardia, hypothermia followed by fever, and potentially death.Therefore, this study aims to evaluate the relationship between the anti- inflammatoryaction of Ang- (1-7) and body temperature in animals submitted to the septic shock model.Two groups of animals will be used: CLP and SHAM (animals that will undergo surgerysimilar to the CLP, however without perforation and connection of the cecum). Bodytemperature, serum concentration of pro-inflammatory cytokines, norepinephrine, nitrate andnitrite, brown adipose tissue and the comparison of survival rates between the twoexperimental groups will be analyzed. We hypothesized that systemic Ang- (1-7)administration could assist in the response against inflammation and, consequently, modulatebrown adipose tissue and minimize hypotension and response to central temperature controlin endotoxemic animals.Male Wistar Hannover rats (300 g) will undergo cannulation surgeries of the right jugularvein and femoral artery (i.v. administration), cecal ligation and puncture (induction of sepsis),in addition to the implantation of the intra-abdominal probe (body temperature records). Therats will receive isotonic saline (0.9%) and Ang- (1-7) (1 mg / kg, i.v.), according to theexperimental protocol. The blood and brown adipose tissue will be collected at differenttimes, according to each experimental protocol, and will be evaluated: pro-inflammatorycytokines by ELISA; nitrate / nitrite by chemiluminescence; NE by liquid chromatographyand the percentage of animal survival by the Kaplan-Meier method. The data will beexpressed as mean ± standard error of the mean, using the software Prism 8.0 (GraphPad).Differences will be considered significant when p <0.05.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PASSAGLIA, PATRICIA; SILVA, HADDER BATISTA; DE JESUS, ALINE ALVES; MARANGA FILHO, MARCO ANTONIO; TRAJANO, ISIS PAIVA; BATALHA, MARCELO EDUARDO; NAVEGANTES, LUIZ CARLOS CARVALHO; BRANCO, LUIZ GUILHERME SIQUEIRA; CARNIO, EVELIN CAPELLARI. Angiotensin-(1-7) improves tail skin heat loss and increases the survival of rats with polymicrobial sepsis. Peptides, v. 167, p. 9-pg., . (16/17681-9, 20/11003-4)

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