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.

Cholinergic stimulation improves electrophysiological rate adaptation during pressure overload-induced heart failure in rats

Analysis of electrophysiology from optical mapping of failing left ventricular myocardium provided insight into the possible therapeutic outcomes of cholinergic stimulation within the left ventricle. Chronic hypothalamic oxytocin neuron activation for downstream cardiac cholinergic neuron stimulation blunted onset of failing electrophysiology induced by pressure overload-induced heart failure in rats.

Carbachol and Nicotine in Prefrontal Cortex Have Differential Effects on Sleep-Wake States

The role of the brainstem cholinergic system in the regulation of sleep-wake states has been studied extensively but relatively little is known about the role of cholinergic mechanisms in prefrontal cortex in the regulation of sleep-wake states. In a recent study, we showed that prefrontal cholinergic stimulation in anesthetized rat can reverse the traits associated with anesthesia and restore a wake-like state, thereby providing evidence for a causal role for prefrontal cholinergic mechanisms in modulating level of arousal. However, the effect of increase in prefrontal cholinergic tone on spontaneous sleep-wake states has yet to be demonstrated. Therefore, in this study, we tested the hypothesis that delivery of cholinergic agonists – carbachol or nicotine – into prefrontal cortex of rat during slow wave sleep (SWS) would produce behavioral arousal and increase the time spent in wake state. We show that unilateral microinjection (200 nL) of carbachol (1 mM) or nicotine (100 mM) into prefrontal cortex during SWS decreased the latency to the onset of wake state (p = 0.03 for carbachol, p = 0.03 for nicotine) and increased the latency to the onset of rapid eye movement sleep (p = 0.008 for carbachol, p = 0.006 for nicotine). Although the infusion of 1 mM carbachol increased the time spent in wake state (p = 0.01) and decreased the time spent in SWS (p = 0.01), infusion of 10 or 100 mM nicotine did not produce any statistically significant change in sleep-wake architecture. These data demonstrate a differential role of prefrontal cholinergic receptors in modulating spontaneous sleep-wake states.

Skin tattooing impairs sweating during passive whole body heating

This study is the first to assess the reflex control of sweating in tattooed skin. The novel findings are twofold. First, attenuated increases in sweat rate were observed in tattooed skin compared with adjacent healthy non-tattooed skin in response to a moderate increase (1.0°C) in internal temperature during a passive whole body heat stress. Second, reduced sweating in tattooed skin is likely related to functional damage to the secretory mechanisms of eccrine sweat glands, rendering it less responsive to cholinergic stimulation.