Relevance of Immune-Sympathetic Nervous System Interplay for the Development of Hypertension

Winklewski, Paweł J.; Radkowski, Marek; Demkow, Urszula

doi:10.1007/5584_2015_169

Cited by 11 publications

(7 citation statements)

References 48 publications

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“…Neural dysregulation may not just accompany but actually precede the progression of BP to diagnostic levels. 15,54 In our work, this possibility was raised by continuing evidence of functional and structural indices of brain dysregulation despite successful lowering of BP in a 1-year medication trial. 14,55 Identifying any process inducing brain dysregulation is challenging, given the complexity of essential hypertension.…”

Section: Discussionmentioning

confidence: 97%

Prehypertensive Blood Pressures and Regional Cerebral Blood Flow Independently Relate to Cognitive Performance in Midlife

Jennings

Muldoon

Ryan

et al. 2017

JAHA

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BackgroundHigh blood pressure is thought to contribute to dementia in late life, but our understanding of the relationship between individual differences in blood pressure (BP) and cognitive functioning is incomplete. In this study, cognitive performance in nonhypertensive midlife adults was examined as a function of resting BP and regional cerebral blood flow (rCBF) responses during cognitive testing. We hypothesized that BP would be negatively related to cognitive performance and that cognitive performance would also be related to rCBF responses within areas related to BP control. We explored whether deficits related to systolic BP might be explained by rCBF responses to mental challenge.Methods and ResultsHealthy midlife participants (n=227) received neuropsychological testing and performed cognitive tasks in a magnetic resonance imaging scanner. A pseudocontinuous arterial spin labeling sequence assessed rCBF in brain areas related to BP in prior studies. Systolic BP was negatively related to 4 of 5 neuropsychological factors (standardized β>0.13): memory, working memory, executive function, and mental efficiency. The rCBF in 2 brain regions of interest was similarly related to memory, executive function, and working memory (standardized β>0.17); however, rCBF responses did not explain the relationship between resting systolic BP and cognitive performance.ConclusionsRelationships at midlife between prehypertensive levels of systolic BP and both cognitive and brain function were modest but suggested the possible value of midlife intervention.

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Section: Discussionmentioning

confidence: 97%

Prehypertensive Blood Pressures and Regional Cerebral Blood Flow Independently Relate to Cognitive Performance in Midlife

Jennings

Muldoon

Ryan

et al. 2017

JAHA

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“…Thus, a vital efferent pathway is compromised in IA. Similarly, dysautonomia involving efferent sympathetic pathways occurs in IMIDs listed in Table 1 [ 207 , 208 , 209 , 210 , 211 , 212 , 213 , 214 , 215 , 216 , 217 , 218 ].…”

Section: β-Ar Promiscuity In the Autoimmune Imid Ra: A Consequencmentioning

confidence: 99%

Sympathetic Nerve Hyperactivity in the Spleen: Causal for Nonpathogenic-Driven Chronic Immune-Mediated Inflammatory Diseases (IMIDs)?

Bellinger

Lorton

2018

IJMS

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Immune-Mediated Inflammatory Diseases (IMIDs) is a descriptive term coined for an eclectic group of diseases or conditions that share common inflammatory pathways, and for which there is no definitive etiology. IMIDs affect the elderly most severely, with many older individuals having two or more IMIDs. These diseases include, but are not limited to, type-1 diabetes, obesity, hypertension, chronic pulmonary disease, coronary heart disease, inflammatory bowel disease, and autoimmunity, such as rheumatoid arthritis (RA), Sjőgren’s syndrome, systemic lupus erythematosus, psoriasis, psoriatic arthritis, and multiple sclerosis. These diseases are ostensibly unrelated mechanistically, but increase in frequency with age and share chronic systemic inflammation, implicating major roles for the spleen. Chronic systemic and regional inflammation underlies the disease manifestations of IMIDs. Regional inflammation and immune dysfunction promotes targeted end organ tissue damage, whereas systemic inflammation increases morbidity and mortality by affecting multiple organ systems. Chronic inflammation and skewed dysregulated cell-mediated immune responses drive many of these age-related medical disorders. IMIDs are commonly autoimmune-mediated or suspected to be autoimmune diseases. Another shared feature is dysregulation of the autonomic nervous system and hypothalamic pituitary adrenal (HPA) axis. Here, we focus on dysautonomia. In many IMIDs, dysautonomia manifests as an imbalance in activity/reactivity of the sympathetic and parasympathetic divisions of the autonomic nervous system (ANS). These major autonomic pathways are essential for allostasis of the immune system, and regulating inflammatory processes and innate and adaptive immunity. Pathology in ANS is a hallmark and causal feature of all IMIDs. Chronic systemic inflammation comorbid with stress pathway dysregulation implicate neural-immune cross-talk in the etiology and pathophysiology of IMIDs. Using a rodent model of inflammatory arthritis as an IMID model, we report disease-specific maladaptive changes in β2-adrenergic receptor (AR) signaling from protein kinase A (PKA) to mitogen activated protein kinase (MAPK) pathways in the spleen. Beta2-AR signal “shutdown” in the spleen and switching from PKA to G-coupled protein receptor kinase (GRK) pathways in lymph node cells drives inflammation and disease advancement. Based on these findings and the existing literature in other IMIDs, we present and discuss relevant literature that support the hypothesis that unresolvable immune stimulation from chronic inflammation leads to a maladaptive disease-inducing and perpetuating sympathetic response in an attempt to maintain allostasis. Since the role of sympathetic dysfunction in IMIDs is best studied in RA and rodent models of RA, this IMID is the primary one used to evaluate data relevant to our hypothesis. Here, we review the relevant literature and discuss sympathetic dysfunction as a significant contributor to the pathophysiology of IMIDs, and then discuss a novel targ...

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“…The heart also exhibits circadian rhythms of metabolic functions governing its activity [243][244][245][246]. The interaction of the phase and amplitude of these various circadian activities within the cardiovascular system sets the appropriate daily growth, repair, hemodynamics, and metabolism of its cells/tissues and, thus, the status of cardiovascular health (or disease) [10,245,[247][248][249][250][251][252][253][254][255][256][257][258][259][260][261][262][263][264]]. As a simple example of postulated pathophysiology emanating from disruption of this circadian interaction, vascular damage is greatest when circadian peaks of cellular/tissue pro-oxidative activities increase and broaden and temporally coincide with such altered (increased and broadened) circadian peaks in pro-inflammatory and vasoconstrictive biological functions-resulting in a maximized prooxidative stimulation of a proinflammatory state.…”

Section: Circadian Rhythm Influence On Human Physiologymentioning

confidence: 99%

Brain Dopamine–Clock Interactions Regulate Cardiometabolic Physiology: Mechanisms of the Observed Cardioprotective Effects of Circadian-Timed Bromocriptine-QR Therapy in Type 2 Diabetes Subjects

Cincotta

2023

IJMS

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Despite enormous global efforts within clinical research and medical practice to reduce cardiovascular disease(s) (CVD), it still remains the leading cause of death worldwide. While genetic factors clearly contribute to CVD etiology, the preponderance of epidemiological data indicate that a major common denominator among diverse ethnic populations from around the world contributing to CVD is the composite of Western lifestyle cofactors, particularly Western diets (high saturated fat/simple sugar [particularly high fructose and sucrose and to a lesser extent glucose] diets), psychosocial stress, depression, and altered sleep/wake architecture. Such Western lifestyle cofactors are potent drivers for the increased risk of metabolic syndrome and its attendant downstream CVD. The central nervous system (CNS) evolved to respond to and anticipate changes in the external (and internal) environment to adapt survival mechanisms to perceived stresses (challenges to normal biological function), including the aforementioned Western lifestyle cofactors. Within the CNS of vertebrates in the wild, the biological clock circuitry surveils the environment and has evolved mechanisms for the induction of the obese, insulin-resistant state as a survival mechanism against an anticipated ensuing season of low/no food availability. The peripheral tissues utilize fat as an energy source under muscle insulin resistance, while increased hepatic insulin resistance more readily supplies glucose to the brain. This neural clock function also orchestrates the reversal of the obese, insulin-resistant condition when the low food availability season ends. The circadian neural network that produces these seasonal shifts in metabolism is also responsive to Western lifestyle stressors that drive the CNS clock into survival mode. A major component of this natural or Western lifestyle stressor-induced CNS clock neurophysiological shift potentiating the obese, insulin-resistant state is a diminution of the circadian peak of dopaminergic input activity to the pacemaker clock center, suprachiasmatic nucleus. Pharmacologically preventing this loss of circadian peak dopaminergic activity both prevents and reverses existing metabolic syndrome in a wide variety of animal models of the disorder, including high fat-fed animals. Clinically, across a variety of different study designs, circadian-timed bromocriptine-QR (quick release) (a unique formulation of micronized bromocriptine—a dopamine D2 receptor agonist) therapy of type 2 diabetes subjects improved hyperglycemia, hyperlipidemia, hypertension, immune sterile inflammation, and/or adverse cardiovascular event rate. The present review details the seminal circadian science investigations delineating important roles for CNS circadian peak dopaminergic activity in the regulation of peripheral fuel metabolism and cardiovascular biology and also summarizes the clinical study findings of bromocriptine-QR therapy on cardiometabolic outcomes in type 2 diabetes subjects.

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Relevance of Immune-Sympathetic Nervous System Interplay for the Development of Hypertension

Cited by 11 publications

References 48 publications

Prehypertensive Blood Pressures and Regional Cerebral Blood Flow Independently Relate to Cognitive Performance in Midlife

Prehypertensive Blood Pressures and Regional Cerebral Blood Flow Independently Relate to Cognitive Performance in Midlife

Sympathetic Nerve Hyperactivity in the Spleen: Causal for Nonpathogenic-Driven Chronic Immune-Mediated Inflammatory Diseases (IMIDs)?

Brain Dopamine–Clock Interactions Regulate Cardiometabolic Physiology: Mechanisms of the Observed Cardioprotective Effects of Circadian-Timed Bromocriptine-QR Therapy in Type 2 Diabetes Subjects

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