Effects of chronic cholinergic stimulation associated with aerobic physical training on cardiac morphofunctional and autonomic parameters in spontaneously hypertensive rats

We investigated hemodynamic, cardiac morphofunctional, and cardiovascular autonomic adaptations in spontaneously hypertensive rats (SHRs) after aerobic physical training associated with chronic cholinergic stimulation. Fifty-four SHRs were divided into two groups: trained and untrained. Each group was further subdivided into three smaller groups: vehicle, treated with pyridostigmine bromide at 5 mg/kg/day, and treated with pyridostigmine bromide at 15 mg/kg/day. The following protocols were assessed: echocardiography, autonomic double pharmacological blockade, heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS). Physical training and pyridostigmine bromide reduced BP and HR and increased vagal participation in cardiac autonomic tonic balance. The associated responses were then potentialized. Treatment with pyridostigmine bromide increased HRV oscillation of both low frequency (LF: 0.2–0.75 Hz) and high frequency (HF: 0.75–3 Hz). However, the association with physical training attenuated HF oscillations. Additionally, treatment with pyridostigmine bromide also increased LF oscillations of BPV. Both treatment groups promoted morphofunctional adaptations, and associated increased ejection volume, ejection fraction, cardiac output, and cardiac index. In conclusion, the association of pyridostigmine bromide and physical training promoted greater benefits in hemodynamic parameters and increased vagal influence on cardiac autonomic tonic balance. Nonetheless, treatment with pyridostigmine bromide alone seems to negatively affect BPV and the association of treatment negatively influences HRV.

Effects of Chronic Cholinergic Stimulation Associated With Aerobic Physical Training on Cardiac Morphofunctional and Autonomic Parameters in Spontaneously Hypertensive Rats

We investigated in spontaneously hypertensive rats (SHR) the hemodynamic, cardiac morphofunctional, and cardiovascular autonomic adaptations after a protocol of aerobic physical training associated with chronic cholinergic stimulation. Fifty-four SRH were divided into two groups: trained and untrained. Afterward, each group was subdivided into three smaller groups: vehicle, treated with pyridostigmine bromide at 5mg/kg/day, and at 15mg/kg/day. The following protocols were assessed: echocardiography, autonomic double pharmacological blockade, analysis of heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS). Physical training and pyridostigmine bromide reduced blood pressure and heart rate and increased vagal participation in cardiac tonic autonomic balance. Associated the responses were potentialized. Pyridostigmine bromide increased the oscillation of low frequency (LF:0.2-0.75Hz) and high frequency (HF:0.75-3Hz) of HRV. However, the association with physical training attenuated HF oscillations. Pyridostigmine bromide also increased LF oscillations of BPV. Both treatments promoted morphofunctional adaptations and associated increased the ejection volume, ejection fraction, cardiac output, and cardiac index. In conclusion, the association of pyridostigmine bromide and physical training promoted greater benefits in hemodynamic parameters and increase vagal influence on cardiac autonomic tonic balance. Nonetheless, pyridostigmine bromide alone seems to negatively affect BPV, while the association of treatment negatively influences HRV.

Interaction between Pyridostigmine Bromide and Oxidative Stress

In this chapter the following topics will be addressed: (1) actions of the cholinergic system in the nervous system, commenting on acetylcholine metabolism and acetylcholinesterase metabolism; (2) acetylcholinesterase inhibitors as subtitle in this topic: pharmacological characterization of pyridostigmine bromide, mechanism of action, and therapeutic effect of the drug; (3) use of pyridostigmine bromide in Persian Gulf War; and (4) potential effect of pyridostigmine bromide in oxidative stress, addressing as subtitle the influence of pyridostigmine bromide on the superoxide-hydrogen peroxide imbalance model. Studies indicate that the interaction between pyridostigmine bromide and stressors could trigger genotoxicity, the mechanism associated with the induction of oxidative stress that leads to this side effect of this drug; however, this discussion needs to be better elucidated and may be more discussed as there is interaction between the pyridostigmine bromide and an endogenous oxidative imbalance caused by it or even by the possible interaction of this with genetic variations present in the antioxidant metabolism.