Experimental dyspnea as a stressor: differential cardiovegetative responses to inspiratory threshold loading in healthy men and women

Dyspnea is associated with an emotional reaction that involves limbic activation. The inspiratory threshold load (ITL) is known to elicit a dyspneic response in healthy subjects. Laboratory-induced stress conditions have been shown to elicit sex-related differences in cardiovascular responses. The aim of this study was to evaluate how healthy men (n = 8) and women (n = 9) react and adapt to 5-min periods of ITL at three levels (low, medium, and high) in terms of heart rate (HR), temporal (RMSSD) and spectral (LF, HF, LF/HF ratio) HRV indexes, and rating of breathing discomfort. HR increased with low, medium, and high ITL in men, whereas it increased only with high ITL in women. LF/HF ratio increased at low ITL in both men and women. Modifications appear to depend essentially on increased LF in men and on reduced HF in women. In addition, HRV modifications differ between men and women, following the order of presentation of ITLs. Our results show a continuous and sustained stress in men (increased HR, LF, and LF/HF ratio across ITL presentation) and a stress adaptation in women. Subjective responses of breathing discomfort were not correlated with sympatho-vagal balance modifications for a subgroup of subjects (n = 10). Breathing against the ITL induced autonomic modifications that are different between men and women, i.e., driven by sympathetic mediated responses in men, whereas women showed a greater parasympathetic modulation of cardiovascular activity. These results highlight the role of the mechanical inspiratory load in the heart rate variability seen in chronic obstructive pulmonary disease.NEW & NOTEWORTHY Breathing against the ITL induced autonomic modifications driven by sympathetic mediated responses in men, whereas women showed a greater parasympathetic modulation of cardiovascular activity, even for low load. A stress circuit could be at the origin of autonomic modifications induced by ITL. Our results would underline the role of the mechanic inspiratory load in the abnormalities in heart rate variability seen in COPD patients

•Bradycardic responses to microinjection of N-methyl-D-aspartate into the nucleus tractus solitarius are inhibited by local activation of 5-HT(3) receptors.

International audienc

The bradycardic and hypotensive responses to serotonin are reduced by activation of GABA A receptors in the nucleus tractus solitarius of awake rats

We investigated the effects of bilateral injections of the GABA receptor agonists muscimol (GABA A) and baclofen (GABA B) into the nucleus tractus solitarius (NTS) on the bradycardia and hypotension induced by iv serotonin injections (5-HT, 2 µg/rat) in awake male Holtzman rats. 5-HT was injected in rats with stainless steel cannulas implanted bilaterally in the NTS, before and 5, 15, and 60 min after bilateral injections of muscimol or baclofen into the NTS. The responses to 5-HT were tested before and after the injection of atropine methyl bromide. Muscimol (50 pmol/50 nl, N = 8) into the NTS increased basal mean arterial pressure (MAP) from 115 ± 4 to 144 ± 6 mmHg, did not change basal heart rate (HR) and reduced the bradycardia (-40 ± 14 and -73 ± 26 bpm at 5 and 15 min, respectively, vs -180 ± 20 bpm for the control) and hypotension (-11 ± 4 and -14 ± 4 mmHg, vs -40 ± 9 mmHg for the control) elicited by 5-HT. Baclofen (12.5 pmol/50 nl, N = 7) into the NTS also increased basal MAP, but did not change basal HR, bradycardia or hypotension in response to 5-HT injections. Atropine methyl bromide (1 mg/kg body weight) injected iv reduced the bradycardic and hypotensive responses to 5-HT injections. The stimulation of GABA A receptors in the NTS of awake rats elicits a significant increase in basal MAP and decreases the cardiac Bezold-Jarisch reflex responses to iv 5-HT injections

Neurons of the A5 region are required for the tachycardia evoked by electrical stimulation of the hypothalamic defence area in anaesthetized rats

In order to assess the possible interactions between the pontine A5 region and the hypothalamic defence area (HDA), we have examined the pattern of double staining for c-Fos protein immunoreactivity (c-Fos-ir) and tyrosine hydroxylase, throughout the rostrocaudal extent of the A5 region in spontaneously breathing anaesthetized male Sprague–Dawley rats during electrical stimulation of the HDA. Activation of the HDA elicited a selective increase in c-Fos-ir with an ipsilateral predominance in catecholaminergic and non-catecholaminergic A5 somata (P < 0.001 in both cases). A second group of experiments was done to examine the importance of the A5 region in modulating the cardiorespiratory response evoked from the HDA. Cardiorespiratory changes were analysed in response to electrical stimulation of the HDA before and after ipsilateral microinjection of muscimol within the A5 region. Stimulation of the HDA evoked an inspiratory facilitatory response, consisting of an increase in respiratory rate (P < 0.001) due to a decrease in expiratory time (P < 0.01). The respiratory response was accompanied by a pressor response (P < 0.001) and tachycardia (P < 0.001). After muscimol microinjection within the A5 region, pressor and heart rate responses to HDA stimulation were reduced (P < 0.01 and P < 0.001, respectively). The respiratory response persisted unchanged. Finally, to confirm functional interactions between the HDA and the A5 region, extracellular recordings of putative A5 neurones were obtained during HDA stimulation. Seventy-five A5 cells were recorded, 35 of which were affected by the HDA (47%). These results indicate that neurones of the A5 region participate in the cardiovascular response evoked from the HDA. The possible mechanisms involved in these interactions are discussed