Hypertension is critically dependent on the carotid body input in the spontaneously hypertensive rat

Abdala, Ana Paula; McBryde, Fiona D; Marina, Nephtalı́; Hendy, Emma B; Engelman, Zoar J.; Fudim, Marat; Sobotka, Paul; Gourine, Alexander V.; Paton, Julian F. R.

doi:10.1113/jphysiol.2012.237800

Cited by 204 publications

(262 citation statements)

References 35 publications

(67 reference statements)

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“…In fact, resection reduced systolic pressure rise over a fivemonth period in SHRs (19). Similar results were observed and published contemporaneously by Paton and colleagues (20). Cur-rently, carotid body resection along with carotid sinus nerve stimulation, vagal nerve stimulation, and renal sympathetic denervation are under consideration as options for treating drug-resistant hypertension and heart failure (21,22).…”

Section: Neural Reflex Interactions Determine Optimal Autonomic Cardisupporting

confidence: 76%

Obstructive sleep apnea and insight into mechanisms of sympathetic overactivity

Abboud¹,

Kumar²

2014

J. Clin. Invest.

120

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Nearly two decades ago, we evaluated ten patients with obstructive sleep apnea (OSA). We determined that alarming nocturnal oscillations in arterial pressure and sympathetic nerve activity (SNA) were caused by regulatory coupling and neural interactions among SNA, apnea, and ventilation. Patients with OSA exhibited high levels of SNA when awake, during normal ventilation, and during normoxia, which contributed to hypertension and organ damage. Additionally, we achieved a beneficial and potentially lifesaving reduction in SNA through the application of continuous positive airway pressure (CPAP), which remains a primary therapeutic approach for patients with OSA. With these results in hindsight, we herein discuss three concepts with functional and therapeutic relevance to the integrative neurobiology of autonomic cardiovascular control and to the mechanisms involved in excessive sympathoexcitation in OSA.

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Section: Neural Reflex Interactions Determine Optimal Autonomic Cardisupporting

confidence: 76%

Obstructive sleep apnea and insight into mechanisms of sympathetic overactivity

Abboud¹,

Kumar²

2014

J. Clin. Invest.

120

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“…The most plausible is a change in the activity of the neurons that regulate the C1 cells. Indeed, abnormal activity within the PVH, the NTS, and the carotid bodies contributes to various forms of hypertension (4,8,192) and heart failure is associated with excessive carotid body activity and changes in the activity of cardiopulmonary and muscle afferents (e.g., 142). A second possible cause of C1 cell hyperactivity, also supported by experimental evidence, may be some change in the local environment of these neurons, perhaps because of microvascular inflammation or glial activation (81,83,89,117,200).…”

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

233

259

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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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“…Carotid sinus denervation (denervation of both carotid body and carotid sinus baroreceptors) prevented the development of hypertension in young prehypertensive spontaneously hypertensive rats and significantly decreased arterial pressure in adult hypertensive spontaneously hypertensive rats. 29 With denervation of the carotid sinus baroreceptors, an increase in arterial pressure might have been expected. However, the aortic baroreceptors were intact, and the arterial pressure decrease supports the view that the peripheral chemoreceptor reflex is hypersensitive in spontaneously hypertensive rats.…”

Section: Carotid Body Modulationmentioning

confidence: 99%

Sympathetic Nervous System and Hypertension

2013

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With the development and implementation of device-based therapeutic interventions to decrease renal and systemic nerve activity in patients with resistant hypertension, there has been an increase in research dealing with the role of the sympathetic nervous system in hypertension. These interventions have produced substantial decreases in blood pressure in patients wherein pharmacological treatments, including agents which inhibit the effects of the renin-angiotensin-aldosterone system, have failed serves to confirm and reassert the essential role of the sympathetic nervous system in hypertension. This review will encompass recent publications dealing with the sympathetic nervous system and hypertension, focusing on those recently published in Hypertension. Sympathetic Activation in Animal Models Obesity-Related HypertensionAlthough there has been a debate as to whether sympathetic activation is a cause or consequence of obesity, the studies noted below support the view that it is the obesity that leads to sympathetic activation. The importance of this sympathetic activation for the development of the hypertension is supported by the finding that renal denervation prevents the development of obesity hypertension in the dog.Studies have now focused on the developmental phase of obesity hypertension regarding the renal sympathoexcitation. In rabbits fed high-fat diets, body weight, plasma insulin and leptin concentrations, mean arterial pressure, heart rate, and renal sympathetic nerve activity were all increased after 1 week.1 Mean arterial pressure and body weight continued to increase over 3 weeks of high-fat diet, whereas heart rate and renal sympathetic nerve activity did not change further. Arterial baroreflex control of renal sympathetic nerve activity was attenuated from the first week of the high-fat diet. Excitatory responses to air jet stress diminished over 3 weeks of high-fat diet. Resumption of normal diet normalized glucose, insulin, leptin, and heart rate, but body weight, visceral fat content, mean arterial pressure, and renal sympathetic nerve activity remained elevated. Increased renal sympathetic nerve activity and its impaired baroreflex control, which occur with 1 week of high-fat feeding, seem integral to the rapid development of obesity hypertension. Increased plasma leptin and insulin may contribute to the initiation of hypertension but are not required for maintenance of the hypertension, which is related to the sustained increase in renal sympathetic nerve activity. As the air jet stress response is transduced by hypothalamic neurons, the authors speculate that this site is involved in the maintenance phase of the hypertension with a sustained increase in renal sympathetic nerve activity.The early effects of diet-induced fat accumulation on lumbar sympathetic nerve activity were also examined in rats over 15 days.2 Increases in brown and white adipose tissue (but not body weight) were accompanied by increases in plasma leptin (but not glucose) concentration and heart rate; however, mean a...

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Hypertension is critically dependent on the carotid body input in the spontaneously hypertensive rat

Cited by 204 publications

References 35 publications

Obstructive sleep apnea and insight into mechanisms of sympathetic overactivity

Obstructive sleep apnea and insight into mechanisms of sympathetic overactivity

C1 neurons: the body's EMTs

Sympathetic Nervous System and Hypertension

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