Exercise training preserves vagal preganglionic neurones and restores parasympathetic tonus in heart failure

Abstract

Exercise training is an efficient tool to attenuate sympathoexcitation, a hallmark of heart failure (HF). Although sympathetic modulation in HF is widely studied, information regarding parasympathetic control is lacking. We examined the combined effects of sympathetic and vagal tonus to the heart in sedentary (Sed) and exercise trained (ET) HF rats and the contribution of respective premotor and preganglionic neurones. Wistar rats submitted to coronary artery ligation or sham surgery were assigned to training or sedentary protocols for 6 weeks. After haemodynamic, autonomic tonus (atropine and atenolol i.v.) and ventricular function determinations, brains were collected for immunoreactivity assays (choline acetyltransferase, ChATir; dopamine β-hydroxylase, DBHir) and neuronal counting in the dorsal motor nucleus of vagus (DMV), nucleus ambiguus (NA) and rostroventrolateral medulla (RVLM). HF-Sed vs. SHAM-Sed exhibited decreased exercise capacity, reduced ejection fraction, increased left ventricle end diastolic pressure, smaller positive and negative dP/dt, decreased intrinsic heart rate (IHR), lower parasympathetic and higher sympathetic tonus, reduced preganglionic vagal neurones and ChATir in the DMV/NA, and increased RVLM DBHir. Training increased treadmill performance, normalized autonomic tonus and IHR, restored the number of DMV and NA neurones and corrected ChATir without affecting ventricular function. There were strong positive correlations between parasympathetic tonus and ChATir in NA and DMV. RVLM DBHir was also normalized by training, but there was no change in neurone number and no correlation with sympathetic tonus. Training-induced preservation of preganglionic vagal neurones is crucial to normalize parasympathetic activity and restore autonomic balance to the heart even in the persistence of cardiac dysfunction.

Maintenance of Blood-Brain Barrier Integrity in Hypertension: A Novel Benefit of Exercise Training for Autonomic Control

“…At the 1st, 2nd, 3rd, 4th, and 5th months chronic catheters (Tygon Tubing, Critchley, Australia: 2 cm of 0.28:0.61 connected to 7 cm of 0.50:1.50 ID:OD) were implanted in the left femoral and left carotid arteries under anesthesia (ketamine, 80 mg/kg plus xylazine, 12 mg/kg, ip ). They were treated sc with analgesic (ketoprofen 1%, 2 mg/kg; Biofarm, Jaboticabal, Brazil) and enrofloxacin (Baytril 5 mg/kg, Bayer Sao Paulo, Brazil) and allowed to recover for 24 h. Time-course changes of resting arterial pressure (AP) were recorded for 30–40 min (computer, 2,000 Hz of sampling frequency, LabChart Pro, ADInstruments Bella Vista, NSW, Australia) on the next day in conscious unrestrained rats, as previously described (Masson et al, 2014 ; Ichige et al, 2016 ). At the 1st, 3rd, and 5th month after AP recordings, 10 kDa fluorescein isothiocyanate dextran (FITC, 10 mg/mL, Sigma Aldrich, USA) plus 70 kDa rhodamine B isothiocyanate dextran (RHO, 10 mg/mL Sigma Aldrich, USA), 286 μL/100 g each, were administered at a slow rate (70 and 300 μL/min in rats aged 1 and 3–5 months, respectively) via the carotid artery and allowed to recirculate for 20 min (Biancardi et al, 2014 ).…”

Subacute pyridostigmine exposure increases heart rate recovery and cardiac parasympathetic tone in rats

“…A similar approach was taken in rats by Ichige et al. where sympathetic tone was calculated as ‘HR after atropine minus intrinsic HR’ and parasympathetic tone as ‘HR after atenolol minus intrinsic HR’ . However, the most important finding regarding pharmacological blockade in the current study was confirmation that the anticipated parasympathomimetic effect of pyridostigmine administration correlated with accelerate heart rate recovery in rats.…”

Augmented fear bradycardia in rats with heart failure

“…While central mechanisms underlying sympathetic hyperactivity in CHF has been extensively studied [21,22], there is scarce information available regarding the effect of CHF on central mechanisms regulating parasympathetic outflows. A study reported that preganglionic parasympathetic neuronal cells were reduced in the nucleus ambiguus and dorsal vagal motor nucleus in rat medulla with CHF when compared with those in healthy controls, explaining the decreased resting parasympathetic tone [23]. Supraspinal cardiovascular regulatory mechanisms may also be involved in parasympathetic hyperresponsiveness to stressors including fear in CHF.…”