Efeitos da exposição à poluição do ar na gestação em ratos normotensos e hipertensos: impacto cardiovascular e neuroimune nas mães e na prole

• Ano de defesa: 2019
• Autor(a) principal: Freitas, Sarah Cristina Ferreira
• Orientador(a): Angelis, Kátia de
• Banca de defesa: Angelis, Kátia de , Zamuner, Stella Regina , Trombetta, Ivani Credidio , Irigoyen, Maria Claudia Costa , Veras, Mariana Matera
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Nove de Julho
• Programa de Pós-Graduação: Programa de Mestrado em Medicina
• Departamento: Saúde
• País: Brasil
• Palavras-chave em Português: poluição do ar; MP2,5; gravidez; prole; pressão arterial; variabilidade autonômica cardiovascular; estresse oxidativo; inflamação
• Palavras-chave em Inglês: air pollution; PM2.5; pregnancy; offspring; blood pressure; cardiovascular autonomic variability; oxidative stress; inflammation
• Área do conhecimento CNPq: CIENCIAS DA SAUDE
• Link de acesso: http://bibliotecatede.uninove.br/handle/tede/2774

Recently, studies have reinforced the relationship of urban pollution, specifically particulate matter smaller than 2.5 μm (PM2.5), with different types of chronic diseases. However, the mechanisms involved in cardiovascular dysfunction associated with PM exposure are still poorly understood. Thus, the objective of this thesis was to evaluate the cardiovascular and neuroimmune effects of daily exposure of MP2,5 during pregnancy in normotensive and hypertensive rats (Wistar and SHR), as well as the effects on their offspring. For this, this thesis was divided into 3 studies. Study 1 - Evaluation of Wistar and SHR pregnant rats not exposed (WC and SHC group) or exposed to air pollution (PM2.5, 600 μg/m3/day) (WE and SHE) (n=7/each). On the twentieth day of gestation, they were cannulated and 24h later arterial pressure (AP) and heart rate (HR) were recorded, followed by euthanasia and the heart was collected for inflammatory and oxidative stress evaluations. Study 2 - Evaluation of newborns of pregnant rats from WC, WE, SHC and SHE groups. HR was recorded by electrocardiogram (n=8) and euthanasia was performed, the heart was collected for inflammatory and oxidative stress evaluations (n=7 pools, with 3 hearts each). Study 3 - Evaluation of offspring of WC and WE rats divided according to gender in WC and WE female groups and WC and WE male groups (n=7/each). After 60 days of weaning, cannulation, AP and HR recording and euthanasia were performed, the heart was collected for inflammatory and oxidative stress evaluations. In study 1, it was possible to observe a reduction in baroreflex sensitivity and an increase in variance of systolic AP in normotensive and hypertensive rats exposed to air pollution when compared with their respective controls. The SAP low frequency band was further increased in the SHE (vs. SHC) group (WC:2.51±0.25, WE:2.91±0.38, SHC:6.62±0.35, SHE: 11.74±1.09 ms2). The WE group was the only one to present elevation of inflammatory cytokines in relation to its control. Oxidative stress assessed by lipoperoxidation and peroxide hydrogen were increased in groups exposed to air pollution compared to control groups. However, the activity of the enzyme NADPH oxidase was increased and the non-enzymatic antioxidant potential (FRAP) was reduced only in the WE group compared to the other 3 experimental groups. In study 2, air pollution caused a reduction in RR variance only in the WE neonates (20.35±3.78 ms2) compared to WC neonates (36.90±3.55 ms2). Regarding inflammation, there was a reduction in IL-10 in the group WE neonates compared to controls and an increase in SHE neonates when compared to the other 3 groups. The SHE neonates group showed increased NADPH oxidase activity and decreased catalase activity compared to the SHC neonates group. In study 3, there was an increase in diastolic and mean AP in WE female and male compared with their controls. WE groups also showed reduction in baroreflex sensitivity, increase in VarSAP and cardiac sympathovagal balance (LF/HF- WC female: 0.29±0.03, WC male: 0.24±0.03, WE female: 0.56±0.09, WE male: 0.47±0.06) compared to controls. Regarding inflammation, there was an increase of IL-6 in WE and IL-10 only in WE female. In conclusion, our results show that exposure to air pollution (PM2.5) only during pregnancy induces cardiovascular, neuroimmune (autonomic and inflammatory) and cardiac oxidative stress dysfunction in normotensive and hypertensive parents, as well as in their offspring, from birth to adulthood, which is probably associated with increased cardiovascular risk.