The Role of Central Nervous System Mechanisms in Resistant Hypertension

Hering, Dagmara; Schlaich, Markus P.

doi:10.1007/s11906-015-0570-0

Cited by 26 publications

(9 citation statements)

References 64 publications

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“…Integrated neural, humoral, and renal mechanisms that collectively mediate increased renal Na ϩ retention and sympathetic nervous system activity have been implicated in the pathogenesis of hypertension (3,23,51,63). The importance of sympathetic nervous system alterations in human and experimental models of hypertension and associated mechanisms have been thoroughly previously reviewed (20,24,51). Of the factors that affect sympathetic activity, activity of the brain renin-angiotensin system (RAS) in cardiovascular regulatory nuclei is pivotal in the pathogenesis of hypertension in most animal models (2,21,69).…”

Section: Introductionmentioning

confidence: 99%

Increased (pro)renin receptor expression in the subfornical organ of hypertensive humans

Cooper

Trivedi

Yamamoto

et al. 2018

American Journal of Physiology-Heart and Circulatory Physiology

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The central nervous system plays an important role in essential hypertension in humans and in animal models of hypertension through modulation of sympathetic activity and Na and body fluid homeostasis. Data from animal models of hypertension suggest that the renin-angiotensin system in the subfornical organ (SFO) of the brain is critical for hypertension development. We recently reported that the brain (pro)renin receptor (PRR) is a novel component of the brain renin-angiotensin system and could be a key initiator of the pathogenesis of hypertension. Here, we examined the expression level and cellular distribution of PRR in the SFO of postmortem human brains to assess its association with the pathogenesis of human hypertension. Postmortem SFO tissues were collected from hypertensive and normotensive human subjects. Immunolabeling for the PRR and a retrospective analysis of clinical data were performed. We found that human PRR was prominently expressed in most neurons and microglia, but not in astrocytes, in the SFO. Importantly, PRR levels in the SFO were elevated in hypertensive subjects. Moreover, PRR immunoreactivity was significantly correlated with systolic blood pressure but not body weight, age, or diastolic blood pressure. Interestingly, this correlation was independent of antihypertensive drug therapy. Our data indicate that PRR in the SFO may be a key molecular player in the pathogenesis of human hypertension and, as such, could be an important focus of efforts to understand the neurogenic origin of hypertension. NEW & NOTEWORTHY This study provides evidence that, in the subfornical organ of the human brain, the (pro)renin receptor is expressed in neurons and microglia cells but not in astrocytes. More importantly, (pro)renin receptor immunoreactivity in the subfornical organ is increased in hypertensive humans and is significantly correlated with systolic blood pressure.

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Section: Introductionmentioning

confidence: 99%

Increased (pro)renin receptor expression in the subfornical organ of hypertensive humans

Cooper

Trivedi

Yamamoto

et al. 2018

American Journal of Physiology-Heart and Circulatory Physiology

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“…In the majority of studies in humans and animal models of hypertension, drugs and interventions can reduce BP and prolong survival rates by activating the parasympathetic nervous system (vagal), by blocking or inhibiting the SNS and the RAS ( 143 – 149 ). Early studies have shown that experimental lesioning of specific circumventricular organs of the forebrain, including the subfornical organ, the anteroventral third ventricle region involving the inferior aspects of the lateral terminalis, prevents the formation of several forms of experimental high BP ( 150 , 151 ). Increasing evidence indicates that the cardiovascular damage caused by overstimulation of the SNS and RAS, their α- and β-adrenergic receptors, and Ang II AT1 receptors is mediated through proinflammatory activation of the immune system ( 152 – 155 ).…”

Section: Potential Role Of the Thymus In Hypertensionmentioning

confidence: 99%

Mechanisms in hypertension and target organ damage: Is the role of the thymus key? (Review)

Dai

Chen

et al. 2018

Int J Mol Med

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A variety of cells and cytokines have been shown to be involved in the whole process of hypertension. Data from experimental and clinical studies on hypertension have confirmed the key roles of immune cells and inflammation in the process. Dysfunction of the thymus, which modulates the development and maturation of lymphocytes, has been shown to be associated with the severity of hypertension. Furthermore, gradual atrophy, functional decline or loss of the thymus has been revealed to be associated with aging. The restoration or enhancement of thymus function via upregulation in the expression of thymus transcription factors forkhead box N1 or thymus transplantation may provide an option to halt or reverse the pathological process of hypertension. Therefore, the thymus may be key in hypertension and associated target organ damage, and may provide a novel treatment strategy for the clinical management of patients with hypertension in addition to different commercial drugs. The purpose of this review is to summarize and discuss the advances in our understanding of the impact of thymus function on hypertension from data from animal and human studies, and the potential mechanisms.

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“…It is commonly thought that a chronic dysregulation of sympathetic outflow, i.e. neurogenic mechanisms based on neuroplasticity and a sensitization of the hypertensive response, may be major underlying causes of resistant hypertension [4,5]. Consequently, novel treatment approaches are needed, which target the chronic dysregulation of central blood pressure control.…”

Section: Is the At2r A Key To Treating Resistant Hypertension?mentioning

confidence: 99%

“…Neurogenic hypertension is not only characterized by sustained sympathoexcitation, but also by impaired baroreflex function [5]. As noted above, and shown in Figure 2, there is a high density of AT2R in the NTS, an area that has a major role in controlling baroreflex function [8,42].…”

Section: At2r and The Baroreflex Functionmentioning

confidence: 99%

Centrally Mediated Cardiovascular Actions of the Angiotensin II Type 2 Receptor

Steckelings

Kloet

Sumners

2017

Trends in Endocrinology & Metabolism

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Sustained increases in activity of the sympathetic neural pathways that exit the brain and which increase blood pressure are a major underlying factor in resistant hypertension. Recently available information on the occurrence of angiotensin II type 2 receptors (AT2R) within or adjacent to brain cardiovascular control centers is consistent with findings that stimulation of these receptors lowers blood pressure, particularly during hypertension of neurogenic origin. Up until recently, brain AT2R had not been considered by many to play a role in the central control of blood pressure. Demonstration of these powerful anti-hypertensive effects of brain AT2R opens the door to reconsideration of their role in blood pressure regulation, and their consideration as a novel therapeutic avenue for resistant hypertension.

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The Role of Central Nervous System Mechanisms in Resistant Hypertension

Cited by 26 publications

References 64 publications

Increased (pro)renin receptor expression in the subfornical organ of hypertensive humans

Increased (pro)renin receptor expression in the subfornical organ of hypertensive humans

Mechanisms in hypertension and target organ damage: Is the role of the thymus key? (Review)

Centrally Mediated Cardiovascular Actions of the Angiotensin II Type 2 Receptor

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