The dorsomedial hypothalamus and the central pathways involved in the cardiovascular response to emotional stress

Fontes, Marco Antônio Peliky; Xavier, Carlos Henrique; Menezes, Rodrigo Cunha Alvim de; DiMicco, Joseph A.

doi:10.1016/j.neuroscience.2011.03.018

Cited by 91 publications

(70 citation statements)

References 112 publications

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“…Our results, thus, indicate that in anesthetized rats, there is a substantial basal sympathetic outflow to the ventricular myocardium. Suppression by atenolol of DMH-induced tachy- cardic responses confirms our previous finding that they are sympathetically mediated (15). Finally, the fact that atenolol suppressed the afterload-independent component of the DMHinduced contractile response indicates that this was also mediated via the cardiac sympathetic outflow.…”

Section: Dmh-induced Chronotropic and Inotropic Responses Are Sympathsupporting

confidence: 87%

“…Our results suggest that the DMH may be involved in the genesis of stress-induced arrhythmias by facilitating sympathetic outflow to the ventricular myocardium. This idea is in accord with the well-established role of the DMH in stress-induced tachycardia in rats (15). Of interest is the fact that supraventricular, but not the ventricular ectopic beats, evoked from DMH were prevented by zatebradine, a blocker of the pacemaker sodium current.…”

Section: Dmh Activation Affects Cardiac Excitabilitysupporting

confidence: 72%

“…Animal experiments conducted during the two last decades provided the basis for understanding these pathways, and it is now firmly established that the dorsomedial hypothalamus (DMH) is a key region in orchestrating neurally mediated cardiovascular responses to stress. Indeed, integrity of synaptic transmission in the DMH is essential for the expression of stress-induced tachycardic and pressor responses (15). These functional studies are well supported by neuroanatomical data: the DMH receives synaptic inputs from many cortical and subcortical areas that are activated during stress and are involved in emotional processing, including the amygdala, the medial prefrontal cortex, and the insular cortex (7,18,34,41).…”

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confidence: 86%

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Asymmetry in the control of cardiac performance by dorsomedial hypothalamus

Xavier

Beig

Ianzer

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Dorsomedial hypothalamus (DMH) plays a key role in integrating cardiovascular responses to stress. We have recently reported greater heart rate responses following disinhibition of the right side of the DMH (R-DMH) in anesthetized rats and greater suppression of stress-induced tachycardia following inhibition of the R-DMH in conscious rats [both compared with similar intervention in the left DMH (L-DMH)], suggesting existence of right/left side asymmetry in controlling cardiac chronotropic responses by the DMH. The aim of the present study was to determine whether similar asymmetry is present for controlling cardiac contractility. In anesthetized rats, microinjections of the GABAA antagonist bicuculline methiodide (BMI; 40 pmol/100 nl) into the DMH-evoked increases in heart rate (HR), left ventricular pressure (LVP), myocardial contractility (LVdP/dt), arterial pressure, and respiratory rate. DMH disinhibition also precipitated multiple ventricular and supraventricular ectopic beats. DMH-induced increases in HR, LVP, LVdP/dt, and in the number of ectopic beats dependent on the side of stimulation, with R-DMH provoking larger responses. In contrast, pressor and respiratory responses did not depend on the side of stimulation. Newly described DMH-induced inotropic responses were rate-, preload- and (largely) afterload-independent; they were mediated by sympathetic cardiac pathway, as revealed by their sensitivity to β-adrenergic blockade. We conclude that recruitment of DMH neurons causes sympathetically mediated positive chronotropic and inotropic effects, and that there is an asymmetry, at the level of the DMH, in the potency to elicit these effects, with R-DMH > L-DMH.

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Section: Dmh-induced Chronotropic and Inotropic Responses Are Sympathsupporting

confidence: 87%

Section: Dmh Activation Affects Cardiac Excitabilitysupporting

confidence: 72%

mentioning

confidence: 86%

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Asymmetry in the control of cardiac performance by dorsomedial hypothalamus

Xavier

Beig

Ianzer

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Previous studies have documented that the DMH is an important node in sympathoexcitatory responses, in particular following psychological stress (for reviews, see refs. 48,52,53). A key component of this stress-induced descending pathway includes the RVLM (33,54,55).…”

Section: Discussionmentioning

confidence: 99%

Arcuate neuropeptide Y inhibits sympathetic nerve activity via multiple neuropathways

Shi¹,

Madden²,

Brooks³

2017

Journal of Clinical Investigation

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Obesity increases sympathetic nerve activity (SNA) via activation of proopiomelanocortin neurons in the arcuate nucleus (ArcN), and this action requires simultaneous withdrawal of tonic neuropeptide Y (NPY) sympathoinhibition. However, the sites and neurocircuitry by which NPY decreases SNA are unclear. Here, using designer receptors exclusively activated by designer drugs (DREADDs) to selectively activate or inhibit ArcN NPY neurons expressing agouti-related peptide (AgRP) in mice, we have demonstrated that this neuronal population tonically suppresses splanchnic SNA (SSNA), arterial pressure, and heart rate via projections to the paraventricular nucleus (PVN) and dorsomedial hypothalamus (DMH The Journal of Clinical Investigation R E S E A R C H A R T I C L E2 8 6 9 jci.org Volume 127 Number 7 July 2017We next tested whether selective excitation or inhibition of ArcN NPY/AgRP neurons alters splanchnic SNA (SSNA), mean AP (MAP), or heart rate (HR) ( Figure 1). As shown in representative experiments ( Figure 1, A and B) and grouped data ( Figure 1C), in ArcN hM3Dq mice, i.p. CNO (0.3 mg/kg) promptly decreased SSNA, MAP, and HR, whereas i.p. saline had no effects. The suppression induced by CNO was sustained for at least 1 hour, and, in mice with longer recordings, up to 4 hours (data not shown). In rats, guinea pigs, and humans, CNO can have nonspecific effects due to its conversion to clozapine (17, 18). However, in WT mice receiving the Cre-dependent hM3Dq vector, neither i.p. saline nor CNO significantly altered these variables, suggesting that CNO was not exerting its effects independently of DREADD activation. A separate group of Agrp-IRES-Cre mice instead received AAV-hM4Di-mCherry in the ArcN (Figure 1, D-F). In these ArcN hM4Di mice, i.p. CNO (0.3 and 1 mg/kg) dose-dependently increased SSNA, MAP, and HR, although the responses developed both NPY-GFP and Cre in AgRP neurons. In agreement with an earlier study using a different approach (14), we found that while not all NPY-GFP neurons had visible hM3Dq-mCherry labeling, 100% of the hM3Dq-mCherry-marked neurons also expressed NPY-GFP (Supplemental Figure 1; supplemental material available online with this article; https://doi.org/10.1172/JCI92008DS1). WT mice never expressed the Cre-dependent DREADD. In a second set of experiments, 2 or more weeks after Agrp-IRES-Cre mice received hM3Dq bilaterally in the ArcN, CNO (0.3 mg/kg) or the saline vehicle was administered i.p., and food intake was monitored for the following 4 hours. As shown previously (14), i.p. CNO, but not saline, rapidly evoked food intake in ArcN hM3Dq mice (Supplemental Figure 1). Conversely, activation of inhibitory DREADDs in ArcN hM4Di mice at the beginning of the feeding period (lights out) inhibited food intake (Supplemental Figure 1). Therefore, we anatomically and functionally confirm that this approach selectively targets ArcN NPY/AgRP neurons. The Journal of Clinical Investigation R E S E A R C H A R T I C L E2 8 7 0jci.org Volume 127 Number 7 July 2017neurons were also observ...

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“…It has been clearly established that the DMH plays a critical role in mediating the cardiovascular and neuroendocrine response to acute (15) and chronic (37) psychological stress. This response may include respiratory effects, as demonstrated by a recent study showing that the DMH mediates tachypnea associated with acute stress responses (7).…”

mentioning

confidence: 99%

Long-lasting bradypnea induced by repeated social defeat

Brouillard

Carrive

Camus

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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peated social defeat in the rat induces long-lasting cardiovascular changes associated with anxiety. In this study, we investigated the effects of repeated social defeat on breathing. Respiratory rate was extracted from the respiratory sinus arrhythmia (RSA) peak frequency of the ECG in rats subjected to social defeat for 4 consecutive days. Respiratory rate was recorded under anesthesia 6 days (Dϩ10) or 26 days (Dϩ30) after social defeat. At Dϩ10, defeated (D) rats spent less time in the open arms of the elevated plus maze test, had heavier adrenal glands, and displayed bradypnea, unlike nondefeated animals. At Dϩ30, all signs of anxiety had disappeared. However, one-half of the rats still displayed bradypnea (D L rats, for low respiratory rate indicated by a lower RSA frequency), whereas those with higher respiratory rate (D H rats) had recovered. Acute blockade of the dorsomedial hypothalamus (DMH) or nucleus tractus solitarii (NTS) 5-HT 3 receptors reversed bradypnea in all D rats at Dϩ10 and in DL rats at Dϩ30. Respiratory rate was also recorded in conscious animals implanted with radiotelemetric ECG probes. DH rats recovered between Dϩ10 and Dϩ18, whereas DL rats remained bradypneic until Dϩ30. In conclusion, social stress induces sustained chronic bradypnea mediated by DMH neurons and NTS 5-HT3 receptors. These changes are associated with an anxiety-like state that persists until Dϩ10, followed by recovery. However, bradypnea may persist in one-half of the population up until Dϩ30, despite apparent recovery of the anxiety-like state.anxiety; breathing; serotonin; social defeat; telemetric recording BREATHING AND ANXIETY ARE intimately related (44). For example, respiratory distress and asphyxia are associated with dreadful feelings, and fear and anxiety can have profound effects on breathing. Clinical studies have shown that panic disorder, characterized by acute and unexpected anxiety attacks and substantial anxiety over the possibility of experiencing further attacks, is associated with symptoms including palpitations, shortness of breath, sweating, and hyperventilation (1). In addition, high levels of anxiety-related behavior in rats are associated with elevation of the resting respiratory rate (9). The respiratory rate also decreases during certain specific responses to stress, for instance during freezing behavior in the rat, when it is associated with ultrasonic vocalizations (19). However, much less is known about the long-term effects of emotional stress on breathing. In adult rats, intense neonatal emotional stress, such as maternal separation, can lead to a decrease in breathing rate during non-rapid-eye-movement sleep (24). A lower respiratory rate was also observed in anesthetized Flinder-Sensitive rats, a well-validated animal model of depression (33). However, respiratory rate does not appear to be altered in patients with major depression, although cardiovascular changes are observed (4). Clearly, more work needs to be done to understand the long-term effects of emotional stress on breathin...

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The dorsomedial hypothalamus and the central pathways involved in the cardiovascular response to emotional stress

Cited by 91 publications

References 112 publications

Asymmetry in the control of cardiac performance by dorsomedial hypothalamus

Asymmetry in the control of cardiac performance by dorsomedial hypothalamus

Arcuate neuropeptide Y inhibits sympathetic nerve activity via multiple neuropathways

Long-lasting bradypnea induced by repeated social defeat

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