Cholinergic Stimulation Improve Renal Inflammation After Myocardial Infarction in Spontaneously Hypertensive Rats

Abstract

IntroductionCardiovascular diseases (CVD) are the leading causes of morbidity and mortality worldwide, and among them, myocardial infarction (MI) has a significant influence on renal function. There is a close relationship between cardiac and renal function, several studies have shown that cardiorenal interactions occur in both directions. This clinical condition, called cardiorenal syndrome, increases the risk of cardiovascular events. It was recently described that the autonomic nervous system (ANS) modulates inflammation, and that vagus nerve stimulation decreases the inflammatory response in different models of septic and aseptic inflammation –this reflex pathway is called as “Cholinergic anti‐inflammatory pathway”. Previous studies by our group have demonstrated that increased vagal activity through administration of pyridostigmine (PY) (acetylcholinesterase pharmacological antagonist) reduces early inflammatory process in myocardial tissue after AMI in normotensive rats, but little is known about vagal modulation and renal inflammation. The aim of this study was to evaluate the effect of cholinergic stimulation on the modulation and expression of the cells inflammatory in renal tissue triggered by AMI in spontaneously hypertensive rats (SHR).Material and MethodsSHR male rats were four groups: SHAM group: S (n = 5), treated group: PY (n=7), infarcted group: I (n = 6) and infarcted and treated group: I + PY (n = 5). All the animals were anesthetized and submitted to thoracotomy and the infarcted and treated groups were subjugated to left coronary artery ligation. Treatment with PY started one hour after thoracotomy, extending until day 7. The total lymphocytes (CD3+) and helper lymphocytes (CD4+) was analysed though immunohistochemistry and expression (TNF‐α, IL‐6, IL‐10) for RT‐qPCR in renal tissue. Statistical analysis, all data were represented as means ± the standard error of the mean (SEM) was performed using GraphPad Prism and one‐way analysis of variance (ANOVA). Values of p> 0.05 were considered statistically significant.ResultsThere were no statistically significant differences in the CD3+ T lymphocytes counts in the renal parenchyma in all four groups. Regarding the CD4+ lymphocytes, the I group showed significant increase lymphocytes than S group (p<0.05). Treatment with PY significantly increased CD4+ lymphocytes group I + PY (p<0.01) when compared with I group. The renal inflammatory profile was confirmed by the significant increase in TNF‐α and IL‐6 mRNA levels (p <0.05), but not IL‐10 when compared to the SHAM group. Treatment with PY significantly decreased the expression of TNF‐α (p <0.01) and IL‐6 (p <0.05) mRNA when compared to the AMI group in renal tissue.ConclusionThe present study demonstrates that cholinergic stimulation with pyridostigmine was able to induces greater anti‐inflammatory cell recruitment and to decrease inflammatory cytokines mRNA expression in renal tissue at day 7 post‐MI in rats.Support or Funding InformationConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Programa de Pós‐Graduação stricto sensu UNINOVE