Cholinergic Stimulation Modulates Kidney Cellular Immune Response Triggered by Myocardial Infarction in Rats
Authors: de Arruda Ribeiro Camila Tur , Granato Daniela Wonraht , Porter Maria Helena Mattos , Silva Jose Antônio , Delle Humberto , Irigoyen Maria Claudia , Colombo Fernanda Marciano Consolim 
Published: June 2021

There is a close relationship between cardiac and renal function, several studies have shown that cardiorenal interactions occur in both directions. Acute myocardial infarction (AMI) has a significant influence on renal function. Changes in renal function may be due to neurohumoral adaptations, reduction of renal perfusion, increase of renal venous pressure and right ventricular dysfunction. More recently, interest has shifted to the role of inflammation in the development of renal lesions. An increase of parasympathetic activity seems to promote changes in the mobilization of inflammatory cells, such as macrophages and lymphocytes. The role of the parasympathetic nervous system in immune cells is known 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.

Objective

The aim of this study was to assess the effects of cholinergic stimulation on the modulation of the cellular immune response triggered by AMI in spontaneously hypertensive rats (SHR).

Material and Methods

Sixteen SHR male rats were randomly assigned to three groups: SHAM group: S (n = 5), 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 infarcted and treated groups were subjugated to left coronary artery ligation. Treatment with PY started one hour after the infarction, extending until day 7. The rats were cannulated in the left femoral artery to record blood pressure on the day 6. On day 7, the animals were euthanized and submitted to organ perfusion and fixation, for immunohistochemical analysis of macrophages (CD‐68+) and lymphocytes (CD3+) in renal tissue. Marked cells were counted in 10 fields including glomerulus and interstitium (Nikon 400x). Statistical analysis was performed using GraphPad Prism and one‐way analysis of variance (ANOVA). Values of p> 0.05 were considered statistically significant.

Results

The I + PY group showed less CD68+ macrophages and more CD3+ T lymphocytes in the renal parenchyma if compared to S and I groups, p = 0.04 and p = 0.04, respectively. The mean levels of systolic blood pressure, diastolic blood pressure and mean arterial pressure found for the I + PY group was lower when compared to the pressure levels found in the other groups.

Conclusion

Cholinergic stimulation using PY was able to quantitatively modify CD68+ macrophages and CD3+ lymphocytes in the renal tissue of rats during the acute phase of the experimental model of AMI. In addition, changes in hemodynamic characteristics were observed with the treatment of this anticholinesterase, suggesting possible protective effects of its vagal immunomodulation.

Support or Funding Information

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Total amount of CD3+ lymphocytes found in the 10 renal fields for the analyzed groups

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Total amount of CD3+ lymphocytes found in the 10 renal fields for the analyzed groups

Total amount of CD68+ macrophages found in the 10 renal fields for the analyzed groups

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Total amount of CD68+ macrophages found in the 10 renal fields for the analyzed groups

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.