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

Abstract

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.

Association of Cardiac Autonomic Responses with Clinical Outcomes of Myasthenia Gravis: Short-Term Analysis of the Heart-Rate and Blood Pressure Variability

“…It has been shown that use of acetylcholine esterase inhibitors is associated with increasing the concentration of acetylcholine both in the synaptic cleft in the neuromuscular junction and in synapses of CNS and autonomic ganglia. Experimental evidence indicates that pyridostygmine improves the autonomic profile, reduces HR at rest, and enhances short-term HRV [38][39][40]. A previous study in spontaneously hypertensive rats showed that cholinergic stimulation with pyridostigmine bromide for 2 weeks reduced BP, HR as well as increased vagal participation in autonomic balance and decreased systolic BPV [38].…”

Altered Cardiac Autonomic Regulation in Individuals with Myasthenia Gravis—A Systematic Review and Meta-Analysis

“…There is evidence of autonomic involvement in individuals with MG [ 6 , 15 ] before and after pharmacological treatment. Cholinergic stimulation induced by AChE inhibitor treatment influences autonomic function, including cardiac function, and improves BRS and HRV in both humans and animal disease models [ 35 , 36 ]. AChE inhibitors also increase the HF while decreasing the LF and sympathovagal balance.…”

Correlation between Cardiovascular Autonomic and Pulmonary Ventilation Functions in Myasthenia Gravis Patients

“…Previous studies have shown that the prolonged use of pyridostigmine enhances cardiac autonomic control, including improvements in vagal tone, BRS, and HRV. In our previous study, we established the presence of diminished cardiovagal tone in MG patients, even as the acetylcholinesterase inhibitors led to an enhancement in vagal tone [17,49]. Considering the evaluation of HRV, future studies could focus on establishing stable therapies for MG before conducting the assessment, maintaining no dose changes for at least 3 months (e.g., corticosteroids).…”