Role of the medial amygdala in mediating responses to aversive stimuli leading to hypertension

Davern, Pamela J.; Head, Geoffrey A.

doi:10.1111/j.1440-1681.2010.05413.x

Cited by 30 publications

(21 citation statements)

References 62 publications

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“…4,20,[35][36][37][38] Given that the present study demonstrates a substantial contribution from the MeAm to maintenance of the hypertensive state in BPH/2J mice, this may prompt more extensive investigation into the role of this and possibly other forebrain regions, which have been suggested to be a major cause of hypertension in humans. …”

Section: Perspectivesmentioning

confidence: 99%

“…34 Hypertension in BPH/2J mice has been likened to that of white-coat hypertensive patients based on SNS hyper-responsivity in addition to exaggerated circadian-related BP surges and cardiovascular hyper-reactivity to stressful situations shown in both BPH/2J mice and white-coat hypertensive patients. 4,20,[35][36][37][38] Given that the present study demonstrates a substantial contribution from the MeAm to maintenance of the hypertensive state in BPH/2J mice, this may prompt more extensive investigation into the role of this and possibly other forebrain regions, which have been suggested to be a major cause of hypertension in humans.…”

Section: Perspectivesmentioning

confidence: 99%

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Major Contribution of the Medial Amygdala to Hypertension in BPH/2J Genetically Hypertensive Mice

et al. 2014

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BPH/2J mice are a genetic model of hypertension developed in the 1970s by Schlager et al.1 These mice were selectively bred for elevated blood pressure (BP) alongside a normotensive (BPN/3J) and hypotensive control strain (BPL/1J), from a base population of 8 inbred strains of mice. Since then a range of pathophysiological factors have been studied to determine the cause of hypertension in BPH/2J mice, and the relatively modest characterization has been increasing in recent years, possibly because of advances in technology used to study mice. 2,3 Our own findings suggest that hypertension in BPH/2J mice is sympathetically mediated, based on the greater depressor response to ganglion blockade, which ultimately abolishes the hypertension in BPH/2J mice and also greater midfrequency mean arterial pressure variability (MAP power). 4 Even the percentage depressor response to ganglion blockade is greater in BPH/2J mice compared with normotensive controls. 4 This contrasts findings in spontaneously hypertensive rats (SHRs) that are likely confounded by a vascular amplifier effect 5 caused by vascular structural changes, which contribute to hypertension in adult SHRs. 6 Recently, we have also reported that BPH/2J mice have renal sympathetic hyperinnervation and enhanced renin synthesis, which results in a greater contribution of the renin-angiotensin system (RAS) to BP maintenance during the dark period of the 24-hour light cycle in BPH/2J mice compared with BPN/3J mice. 7 Early studies indicated that BPH/2J mice have aberrant brain catecholamine levels, 8 suggesting that the hypertension may be centrally mediated. Furthermore, using Fos as a marker of neuronal activity, BPH/2J mice were also shown to have greater neuronal activity in key cardiovascular regulatory brain regions compared with normotensive control BPN/3J mice. 4 Importantly, of the limbic, hypothalamic, and medullary brain regions analyzed using Fos immunohistochemistry, the medial amygdala (MeAm) was the only region to show greater neuronal activity during the light (inactive) and the dark (active) period in BPH/2J compared with BPN/3J mice, 4 suggesting that this region may be inherently overactive in BPH/2J mice. Furthermore, neuronal activity within the MeAm correlated strongly with BP level (R=0.98), suggesting that neuronal activity in the MeAm may be related to BP level. 4 The MeAm is an important limbic region that integrates sensory information, including stress and fear as well as reproductive-related inputs, and regulates the subsequent cardiovascular, behavioral, and hormonal responses.9-11 The MeAm is activated by stressful stimuli particularly of psychological rather than a physiological nature 12 and is involved Abstract-BPH/2J mice are recognized as a neurogenic model of hypertension primarily based on overactivity of the sympathetic nervous system and greater neuronal activity in key autonomic cardiovascular regulatory brain regions. The medial amygdala (MeAm) is a forebrain region that integrates the autonomic response...

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Section: Perspectivesmentioning

confidence: 99%

Section: Perspectivesmentioning

confidence: 99%

Major Contribution of the Medial Amygdala to Hypertension in BPH/2J Genetically Hypertensive Mice

et al. 2014

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“…The findings in these animals are highly applicable to humans who respond inappropriately to normal daily stressors, including chronic stress, fear, anxiety, phobias, and panic attacks. Thus, genetic changes to the amygdala and hypothalamus in this mouse, which cause inappropriate activation of the SNS during the activities of normal life, can induce a form of hypertension that compresses the time frame of the human experience of decades [16].…”

Section: Introductionmentioning

confidence: 99%

New Approaches to Quantifying Sympathetic Nerve Activity

2011

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The importance of the sympathetic nervous system in the pathophysiology of human and experimental models of hypertension is well established. Underpinning recent advances has been direct recording from sympathetic nerves via implanted electrodes in animals or microneurography in human subjects. However, the limited life of a recording electrode and the prolonged nature of the development of hypertension bring with it the difficulty of comparing sympathetic nerve activity between groups. New developments in high-frequency radiotelemetry in animals have heralded a new age in long-term sympathetic recordings ideal for hypertension research. Standard multifiber recordings in human and animal studies have provided information about the frequency and amplitude of sympathetic bursts. Characterization of sympathetic output is now possible from new techniques of determining single-unit firing frequency, firing probability, and the number of spikes generated per cardiac interval. These have led to a better understanding of sympathoactivation in hypertension and its underlying mechanisms.

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“…Moreover, a decrease in heart rate (HR) variability (27) and baroreflex sensitivity (BRS) (51) as well as an exaggerated cardiovascular response to stress have been described under these pathological conditions (10,11,49) and associated with higher cardiovascular risk (13,78).…”

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confidence: 99%

Autonomic cardiocirculatory control in mice with reduced expression of the vesicular acetylcholine transporter

Durand

Becari

Tezini

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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In cardiovascular diseases, sympathetic tone has been comprehensively studied, whereas parasympathetic tone has received minor attention. The vesicular ACh transporter (VAChT) knockdown homozygous (VAChT KD HOM ) mouse is a useful model for examining the cardiocirculatory sympathovagal balance. Therefore, we investigated whether cholinergic dysfunction caused by reduced VAChT expression could adversely impact hemodynamic parameter [arterial pressure (AP) and heart rate (HR)] daily oscillation, baroreflex sensitivity, hemodynamic variability, sympathovagal balance, and cardiovascular reactivity to restraint stress. Wild-type and VAChT KD HOM mice were anesthetized for telemetry transmitter implantation, and APs and HRs were recorded 10 days after surgical recovery. Changes in HR elicited by methylatropine and propranolol provided the indexes of sympathovagal tone. Cardiovascular reactivity in response to a restraint test was examined 24 h after continuous recordings of AP and HR. VAChT KD HOM mice exhibited reduced parasympathetic and elevated sympathetic tone. Daily oscillations of AP and HR as well as AP variability were similar between groups. Nevertheless, HR variability, patterns with two dissimilar variations from symbolic analysis, and baroreflex sensitivity were reduced in VAChT KD HOM mice. The change in mean AP due to restraint stress was greater in VAChT KD HOM mice, whereas the tachycardic response was not. These findings demonstrate that the cholinergic dysfunction present in the VAChT KD HOM mouse did not adversely impact basal hemodynamic parameters but promoted autonomic imbalance, an attenuation of baroreflex sensitivity, and a greater pressure response to restraint stress. These results provide a framework for understanding how autonomic imbalance impacts cardiovascular function. daily hemodynamic oscillations; heart rate variability; mice; parasympathetic nervous system; vesicular acetylcholine transporter IN A NUMBER of cardiovascular diseases, e.g., heart failure, one of the most important changes to maintain cardiac output is sympathetic overactivity (79). This outcome is accompanied by a reduction in parasympathetic tone (47). Derangement of the autonomic nervous system seems to contribute to cardiac dysfunction and remodeling (17). However, although control of sympathetic tone in cardiovascular diseases has been extensively studied, less attention has been given to the role played by parasympathetic function (47).Regulation of cholinergic activity in the heart has recently emerged as an important step in the preservation of long-term cardiac function (64). Indeed, recent epidemiological evidence suggests improved outcomes for cardiovascular diseases in patients with Alzheimer's disease receiving anticholinesterase treatment (40,46). In addition, studies using acetylcholinesterase inhibitors in animals and patients with heart failure have demonstrated that it may be potentially useful for cardiovascular protection, resulting in beneficial effects for markers of cardiovascular risk and dysfu...

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Role of the medial amygdala in mediating responses to aversive stimuli leading to hypertension

Cited by 30 publications

References 62 publications

Major Contribution of the Medial Amygdala to Hypertension in BPH/2J Genetically Hypertensive Mice

Major Contribution of the Medial Amygdala to Hypertension in BPH/2J Genetically Hypertensive Mice

New Approaches to Quantifying Sympathetic Nerve Activity

Autonomic cardiocirculatory control in mice with reduced expression of the vesicular acetylcholine transporter

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