Efeitos da estimulação colinérgica na modulação da inflamação cardiorrenal após infarto do miocárdio em ratos espontaneamente hipertensos (SHR)

• Autor(a) principal: Fonseca, Maria Helena Mattos Porter
• Data de Publicação: 2020
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da Uninove
• Texto Completo: http://bibliotecatede.uninove.br/handle/tede/2765
• topic: infarto agudo do miocárdio; estimulação colinérgica; inflamação renal; fisiopatologia; acute myocardial infarction; cholinergic stimulation; renal inflammation; physiopathology; CIENCIAS DA SAUDE

INTRODUCTION: Renal inflammation occurs early after AMI with a worst cardiovascular prognosis associated. The inflammatory process is modulated by the activity of the autonomic nervous system, and the parasympathetic efferent pathway has an anti-inflammatory role already recognized (anti-inflammatory cholinergic reflex). Previous studies have demonstrated improvement of the anti-inflammatory profile in the heart of normotensive rats after AMI. Information on the impact of cholinergic stimulation on acute renal inflammation after AMI is scarce. OBJECTIVE: Evaluate the effects of vagal stimulation, by administering pyridostigmine bromide (PY), on renal inflammatory response and morphofunctional parameters of the heart of SHR rats (spontaneously hypertensive rats) 7 days after AMI. METHODS: SHR male rats were randomized into three groups: SHAM (thoracotomy group), MI (infarcted group submitted to ligation of the left coronary artery) and MI+PY group (infarcted group and treated with PY at a dose of 40mg/Kg/day, for 7 days started on the day of AMI). All animals were submitted to cannulation of the left femoral artery at the 5th of after AMI, and on the next day direct blood pressure curves were made for subsequent analysis of hemodynamic variables and heart rate variability (HRV) in time and frequency domains. The Ecodopplercardiogram was performed on the 6th day to obtain morphofunctional parameters of the heart, and on the 7th day the rats were euthanized for tissue collection. RESULTS: The MI group, when compared to the SHAM group, showed significant changes (p<0.001): lower values of systolic and diastolic pressure; larger systolic and diastolic diameters of the left ventricle (LV); systolic dysfunction, characterized by the lower ejection fraction of the LV and the lower fractional variation of the LV area (FAC); diastolic dysfunction, evidenced by higher ventricular filling pressure (E/A ratio); and autonomous unbalance, with higher sympathetic activity quantified by the higher LF/HF ratio. There were no significant differences in the number of immune cells (macrophages and lymphocytes) between the MI and SHAM groups. The MI group showed higher activation of pro-inflammatory genes (IL1-β and TNF-α) as well as the TGF-β gene. The infarcted group treated with PY showed: higher vagal modulation, evidenced by HRV in both domains of time and frequency, greater sensitivity of the baroreflex, inferred by the higher alpha-index value, compared to the two other groups; smaller systolic and diastolic diameters of the LV and lower E/A ratio, with higher FAC, compared to the MI group, indicating reduction of morphofunctional changes related to AMI; increased genic expression of anti-inflammatory cytokines (IL-10 and IL-13), IL-17A and chemokine MCP-1 compared to the other groups; and reduction of gene expression of pro-inflammatory cytokines (IL1-β and TNF-α) (p<0.05). TGF-β increased expression in both infarcted groups, being more expressive in the IM group (p<0.01). CONCLUSION: Our results showed that cholinergic stimulation, through the administration of PY, was able to reduce cardiac morphofunctional changes and also reduce inflammation in renal tissue after AMI in SHR rats. These results support the concept that the cholinergic system can be a possible therapeutic target in the treatment of local and systemic changes in AMI. Keywords: Acute Myocardial