Sustained suppression of sympathetic activity and arterial pressure during chronic activation of the carotid baroreflex

Lohmeier, Thomas E.; Iliescu, Radu; Dwyer, Terry; Irwin, Eric D.; Cates, Adam W.; Rossing, Martin A.

doi:10.1152/ajpheart.00372.2010

Cited by 90 publications

(97 citation statements)

References 25 publications

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“…An increase in the resting activity of the C1 cells and other presympathetic neurons of the RVLM could plausibly contribute to the increased SNA in such diseases (9,78). Chronic baroreceptor stimulation, which presumably decreases the activity of the C1 cells in the conscious state as under anesthesia, produces a sustained AP reduction in experimental animals and in humans with drug-refractory essential hypertension (106). In human heart failure, the overflow of catecholamine metabolites from the brain is enhanced suggesting that the release of CNS norepinephrine, and possibly epinephrine, is elevated (94).…”

Section: C1 Cells and Diseasementioning

confidence: 99%

C1 neurons: the body's EMTs

Guyenet

Stornetta

Bochorishvili

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

243

262

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The C1 neurons reside in the rostral and intermediate portions of the ventrolateral medulla (RVLM, IVLM). They use glutamate as a fast transmitter and synthesize catecholamines plus various neuropeptides. These neurons regulate the hypothalamic pituitary axis via direct projections to the paraventricular nucleus and regulate the autonomic nervous system via projections to sympathetic and parasympathetic preganglionic neurons. The presympathetic C1 cells, located in the RVLM, are probably organized in a roughly viscerotopic manner and most of them regulate the circulation. C1 cells are variously activated by hypoglycemia, infection or inflammation, hypoxia, nociception, and hypotension and contribute to most glucoprivic responses. C1 cells also stimulate breathing and activate brain stem noradrenergic neurons including the locus coeruleus. Based on the various effects attributed to the C1 cells, their axonal projections and what is currently known of their synaptic inputs, subsets of C1 cells appear to be differentially recruited by pain, hypoxia, infection/inflammation, hemorrhage, and hypoglycemia to produce a repertoire of stereotyped autonomic, metabolic, and neuroendocrine responses that help the organism survive physical injury and its associated cohort of acute infection, hypoxia, hypotension, and blood loss. C1 cells may also contribute to glucose and cardiovascular homeostasis in the absence of such physical stresses, and C1 cell hyperactivity may contribute to the increase in sympathetic nerve activity associated with diseases such as hypertension. C1 neurons; blood pressure; brain stem BEST KNOWN for their contribution to the control of arterial pressure (AP), the C1 neurons have also been implicated in many other physiological processes ranging from neuroendocrine responses to infection and inflammation, glucose homeostasis, reproduction, breathing, thermoregulation, hypothalamo-pituitary axis (HPA)-mediated stress responses, and food consumption. The purpose of this review is to summarize the most salient information concerning the C1 cells, to point out some of the remaining gaps in our current knowledge, and to suggest a few unifying physiological principles that could account for these seemingly disparate observations. Based on the various effects attributed to the C1 cells and what is currently known of their synaptic inputs, we propose that these neurons are, figuratively speaking, the body's "emergency medical technicians." By this we imply that these neurons produce stereotyped autonomic, metabolic, and neuroendocrine responses designed to help the organism survive major acute physical stresses such as accidental, pathological, or dive-related hypoxia or physical injury and its associated cohort of acute infection, blood loss, and hypotension. These emergency responses include, in the short term and depending on the stress, vasoconstriction, cardioinhibition, or acceleration, breathing stimulation, antidiuresis, changes in metabolism, and gastrointestinal (GI) functions designed to conserve pe...

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Section: C1 Cells and Diseasementioning

confidence: 99%

C1 neurons: the body's EMTs

Guyenet

Stornetta

Bochorishvili

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

243

262

View full text Add to dashboard Cite

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“…10 At the same time, they suggested that renal nerves are not the only mechanism because renal denervation does not abolish sustained reduction in AP during baroreflex activation. 47 While electrical activation of the carotid baroreflex does not seem to disrupt the native baroreflex function, 48 examining the baroreflex equilibrium diagram after baroreflex activation therapy in an animal model of hypertension might provide further information as to…”

Section: Clinical Implicationmentioning

confidence: 99%

Predominant Role of Neural Arc in Sympathetic Baroreflex Resetting of Spontaneously Hypertensive Rats

Sata

Kawada

Shimizu

et al. 2015

Circ J

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592SATA Y et al. Circulation JournalOfficial Journal of the Japanese Circulation Society http://www. j-circ.or.jp classified as a short-term blood pressure control system, 8 carotid baroreflex activation therapy has succeeded in reducing blood pressure in patients with resistant hypertension for more than 1 year, 9 suggesting a potential role of the arterial baroreflex in the long-term regulation of blood pressure. 10 Considering the multifactorial and complex nature of hypertension, further research is needed to understand how sympathetic nerve activity (SNA) and AP are determined in hypertension. The arterial baroreflex system constitutes a key link between the autonomic nervous system and the cardiovascular system. The reflex arc of baroreflex can be divided into 2 principal arcs: the neural arc from pressure input to SNA, and the peripheral arc from SNA to AP. 11,12 Under normal physiological conditions, because the arterial baroreflex operates as a closedloop feedback control system, it is difficult to separately quantify neural and peripheral arc characteristics.The behavior of a system might be described by dynamic and static characteristics. The dynamic characteristics determine he arterial baroreflex control of arterial pressure (AP) is known to reset to a higher input pressure range in hypertension. 1 To cope with the resetting, carotid baroreflex activation is proposed as a potential treatment of drugresistant hypertension. 2,3 Involvement of both neural and cardiovascular factors has been proposed in the pathophysiology of hypertension. Previous studies have demonstrated that sympathetic outflow from the central nervous system is increased in spontaneously hypertensive rats (SHR). 4,5 Peripheral factors such as cardiac hypertrophy and increased vascular resistance are also considered responsible for high AP in SHR. 6 Abnormality in vascular function is also reported in hypertensive patients. 7 Editorial p 510Device-based neuromodulation therapy has increasingly drawn scientific interest. While the arterial baroreflex has been Background: There is ongoing controversy over whether neural or peripheral factors are the predominant cause of hypertension. The closed-loop negative feedback operation of the arterial baroreflex hampers understanding of how arterial pressure (AP) is determined through the interaction between neural and peripheral factors.

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“…105 In his original study, Thrasher (2002) showed that unloading of baroreceptors at one carotid sinus (with all other arterial baroreceptors denervated) caused a sustained pressor response lasting up to 3 weeks in conscious dogs. 105 Lohmeier et al 106 electrically stimulated the carotid sinus directly and also showed reductions in arterial pressure for up to 3 weeks. Subsequently, carotid sinus stimulation has been performed in humans with hypertension.…”

Section: Drug-resistant Hypertension-how To Treat?mentioning

confidence: 99%

The sympathetic nervous system and blood pressure in humans: implications for hypertension

2011

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A neurogenic component to primary hypertension (hypertension) is now well established. Along with raised vasomotor tone and increased cardiac output, the chronic activation of the sympathetic nervous system in hypertension has a diverse range of pathophysiological consequences independent of any increase in blood pressure. This review provides a perspective on the actions and interactions of angiotensin II, inflammation and vascular dysfunction/brain hypoperfusion in the pathogenesis and progression of neurogenic hypertension. The optimisation of current treatment strategies and the exciting recent developments in the therapeutic targeting of the sympathetic nervous system to control hypertension (for example, catheter-based renal denervation and carotid baroreceptor stimulation) will be outlined. Keywords: sympathetic nerve activity; neurogenic hypertension; immune-to-brain signalling The sympathetic renaissancePrimary (or essential) hypertension (termed hypertension from here on) accounts for the vast majority of hypertensive cases (B95%).1 Although the aetiology of this condition is incompletely understood, it appears that along with genetic factors, several environmental and behavioural 'hypertensiogenic' factors have been identified, such as obesity, insulin resistance, high-salt intake, low physical activity levels and stress.1 Given the elevated risk of stroke, renal failure, myocardial infarction and coronary heart disease in those afflicted with high blood pressure, the elucidation of the key pathogenic features and optimisation of effective therapeutic strategies are critical.The most common form of hypertension is neurogenic hypertension, defined as high blood pressure with sympathetic overdrive, loss of parasympathetically mediated cardiac variability and excessive angiotensin II (Ang II) activity.2 The importance of the sympathetic nervous system in the short-term regulation of blood pressure via the modulation of peripheral vascular tone and cardiac output is well established, while the role of the sympathetic nerve activity (SNA) in long-term blood pressure control is more controversial. [3][4][5] Although the concept of a potential neurogenic component to hypertension is not new, 4 it has perhaps received less attention than the renin-angiotensin system (RAS), which has been a prominent therapeutic and research target in hypertension over the past few decades. Nevertheless, the activation of the sympathetic nervous system and the RAS in hypertension appears inextricably, and reciprocally, linked. Evidence from studies in both patients and animal models of hypertension strongly implicate the chronic sympathetic neural activation in the aetiology and progression of hypertension (Figure 1). 2,[6][7][8][9] The use of regional surgical sympathectomy to treat hypertension over 50 years ago before the availability of antihypertensive medications that lower sympathetic activity provides an early indication of the clinical appreciation for a significant neurogenic component to hypertension.10 Recent clini...

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Sustained suppression of sympathetic activity and arterial pressure during chronic activation of the carotid baroreflex

Cited by 90 publications

References 25 publications

C1 neurons: the body's EMTs

C1 neurons: the body's EMTs

Predominant Role of Neural Arc in Sympathetic Baroreflex Resetting of Spontaneously Hypertensive Rats

The sympathetic nervous system and blood pressure in humans: implications for hypertension

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