Asymmetric sympathetic output: The dorsomedial hypothalamus as a potential link between emotional stress and cardiac arrhythmias

Fontes, Marco Antônio Peliky; Filho, Marcelo Limborço; Machado, Natalia; Paula, Cristiane Amorim de; Cordeiro, Letícia Maria de Souza; Xavier, Carlos Henrique; Marins, Fernanda Ribeiro; Henderson, Luke A.; Macefield, Vaughan G.

doi:10.1016/j.autneu.2017.01.001

Cited by 24 publications

(13 citation statements)

References 74 publications

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“…This finding supports the modulation of medullary baroreflex circuitry by supramedullary regions within the midbrain and diencephalon [67]. These regions are recruited during emotional/psychological stresses [33,68] to provide excitatory inputs into the rostral ventromedial [62] and ventrolateral medullary neurons regulating heart and vasomotion [50,68]. These overactivated central regions express a2-adrenoreceptors and I1 imidazoline receptors, which are targets for the centrally acting antihypertensives [69,70] being assessed in the present study.…”

Section: Discussionsupporting

confidence: 84%

Centrally acting antihypertensives change the psychogenic cardiovascular reactivity

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Costa

Moraes

et al. 2021

Fundamemntal Clinical Pharma

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Clonidine (CL) and Rilmenidine (RI) are among the most frequently prescribed centrally acting antihypertensives. Here, we compared CL and RI effects on psychogenic cardiovascular reactivity to sonant, luminous, motosensory, and vibrotactile stimuli during neurogenic hypertension. The femoral artery and vein of Wistar (WT – normotensive) and spontaneously hypertensive rats (SHR) were catheterized before (24 h interval) i.p. injection of vehicle (NaCl 0.9%, control ‐ CT group), CL (10 µg/kg), or RI (10 µg/kg) and acute exposure to luminous (5000 lm), sonant (75 dB sudden tap), motor (180° cage twist), and air‐jet (10 L/min – restraint and vibrotactile). Findings showed that: (i) CL or RI reduced the arterial pressure of SHR, without affecting basal heart rate in WT and SHR; (ii) different stimuli evoked pressor and tachycardic responses; (iii) CL and RI reduced pressor response to sound; (iv) CL or RI reduced pressor responses to luminous stimulus without a change in peak tachycardia in SHR; (v) cage twist increased blood pressure in SHR, which was attenuated by CL or RI; (vi) air‐jet increased pressure and heart rate; (vii) CL or RI attenuated the pressor responses to air‐jet in SHR while RI reduced the chronotropic reactivity in both strains. Altogether, both antihypertensives relieved the psychogenic cardiovascular responses to different stimuli. The RI elicited higher cardioprotective effects through a reduction in air‐jet‐induced tachycardia.

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Section: Discussionsupporting

confidence: 84%

Centrally acting antihypertensives change the psychogenic cardiovascular reactivity

Mendonça

Costa

Moraes

et al. 2021

Fundamemntal Clinical Pharma

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“…We recently examined functional changes in the brain during experimental muscle pain, induced by a 40-min infusion of hypertonic saline into a leg muscle, which causes a sustained increase in MSNA in some participants but a sustained decrease in others; the pattern is reproducible in a given individual and we recently showed that those in whom MSNA increased during tonic muscle pain exhibited increases in BOLD signal intensity in several areas (Kobuch et al, 2017(Kobuch et al, , 2018, including the anterior insula and anterior medial prefrontal cortex (mPFC) on the left, and dlPFC and anterior cingulate cortex (ACC) on the right, while signal intensity decreased in the mPFC and dlPFC on the left (Figure 5). We also saw an increase in signal intensity in the left DMH, which fits with the role of this nucleus in the generation of autonomic responses to stress (DiMicco et al, 2002;Fontes et al, 2017). A brainstem-specific analysis also showed differential responses, with increases in BOLD signal intensity in RVLM and dlPons, as well as NTS (not shown), in the group exhibiting an increase in MSNA, while activity in the midbrain PAG only showed a sustained increase in the group in whom MSNA fell (Figure 6).…”

Section: Changes In Msna-coupled Bold Signal Intensity During Physiolsupporting

confidence: 80%

Identifying Increases in Activity of the Human RVLM Through MSNA-Coupled fMRI

Macefield

Henderson

2020

Front. Neurosci.

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Aim: We initially developed concurrent recording of muscle sympathetic nerve activity (MSNA) and functional magnetic resonance imaging (fMRI) of the brain to functionally identify the human homolog of the rostral ventrolateral medulla (RVLM). Here we summarize the cortical and subcortical connections to the RVLM, as identified using MSNA-coupled fMRI. Methods: MSNA was recorded via tungsten microelectrodes inserted into the peroneal nerve. Gradient echo, echo-planar fMRI was performed at 3T (Philips Achieva). 200 volumes (46 axial slices (TR = 8 s, TE = 4 s, flip angle = 90 • , raw voxel size = 1.5 × 1.5 × 2.75 mm) were collected in a 4 sON , 4 s-OFF sparse sampling protocol and MSNA measured in each 1 s epoch in the 4-s period between scans. Blood oxygen level dependent (BOLD) signal intensity was measured in the corresponding 1 s epoch 4 s later to account for peripheral neural conduction and central neurovascular coupling delays. Results: BOLD signal intensity was positively related to bursts of MSNA in the RVLM, dorsomedial hypothalamus (DMH), ventromedial hypothalamus (VMH), insula, dorsolateral prefrontal cortex (dlPFC), posterior cingulate cortex (PCC), and precuneus, and negatively related in the caudal ventrolateral medulla (CVLM), nucleus tractus solitarius (NTS), and the midbrain periaqueductal gray (PAG). During physiological increases in MSNA (tonic muscle pain), MSNA-coupled BOLD signal intensity was greater in RVLM, NTS, PAG, DMH, dlPFC, medial prefrontal cortex (mPFC), precuneus, and anterior cingulate cortex (ACC) than at rest. During pathophysiological increases in MSNA [obstructive sleep apnoea (OSA)] signal intensity was also higher in dlPFC, mPFC, ACC, and precuneus than in controls. Conversely, signal intensity was lower in RVLM in OSA than in controls, which we interpret as reflecting a withdrawal of active inhibition of the RVLM. Conclusion: These results suggest that multiple cortical and subcortical areas are functionally coupled to the RVLM, which in turn is functionally coupled to the generation of spontaneous bursts of MSNA and their augmentation during physiological and pathophysiological increase in vasoconstrictor drive.

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“…Multiple areas of the brain project to the DMH 44 and we found that many provide input to DMH Brs3 →RPa neurons. Suprahypothalamic input to the DMH possibly mediates autonomic responses to stress 35,45,46 . However, we did not observe substantial cortical input to DMH Brs3 →RPa neurons, suggesting that they are not central to this response.…”

Section: Discussionmentioning

confidence: 99%

Brs3 neurons in the mouse dorsomedial hypothalamus regulate body temperature, energy expenditure, and heart rate, but not food intake

Piñol

Zahler

et al. 2018

Nat Neurosci

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Bombesin-like receptor 3 (BRS3) is an orphan G protein-coupled receptor that regulates energy homeostasis and heart rate. We report that acute activation of Brs3 -expressing neurons in the dorsomedial hypothalamus (DMH Brs3 ) increased body temperature (Tb), brown adipose tissue temperature, energy expenditure, heart rate and blood pressure, with no effect on food intake or physical activity. Conversely, activation of Brs3 neurons in the paraventricular nucleus of the hypothalamus (PVH Brs3 ) had no effect on Tb or energy expenditure, but suppressed food intake. Inhibition of DMH Brs3 neurons decreased Tb and energy expenditure, suggesting a necessary role in Tb regulation. We found that the preoptic area provides major input (excitatory and inhibitory) to DMH Brs3 neurons. Optogenetic stimulation of DMH Brs3 projections to the raphe pallidus (RPa) increased Tb. Thus, DMH Brs3 →RPa neurons regulate Tb, energy expenditure and heart rate, and PVH Brs3 neurons regulate food intake. Brs3 expression is a useful marker for delineating energy metabolism regulatory circuitry.

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Asymmetric sympathetic output: The dorsomedial hypothalamus as a potential link between emotional stress and cardiac arrhythmias

Cited by 24 publications

References 74 publications

Centrally acting antihypertensives change the psychogenic cardiovascular reactivity

Centrally acting antihypertensives change the psychogenic cardiovascular reactivity

Identifying Increases in Activity of the Human RVLM Through MSNA-Coupled fMRI

Brs3 neurons in the mouse dorsomedial hypothalamus regulate body temperature, energy expenditure, and heart rate, but not food intake

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