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Current Cardiology Reports Sep 2019Sympathetic overactivity plays an important role in the progression of pulmonary arterial hypertension (PAH). The purpose of this review is to illustrate localization of... (Review)
Review
PURPOSE OF REVIEW
Sympathetic overactivity plays an important role in the progression of pulmonary arterial hypertension (PAH). The purpose of this review is to illustrate localization of pulmonary arterial sympathetic nerves, the key steps of pulmonary artery denervation (PADN) procedure, and to highlight clinical outcomes.
RECENT FINDINGS
Sympathetic nerves mostly occurred in the posterior region of the bifurcation and pulmonary trunk. Emerging preclinical data provided the potential of PADN for PAH. PADN, produced at bifurcation area, improved a profound reduction of pulmonary arterial pressure and ameliorated clinical outcomes with an exclusive ablation catheter. The application of PADN in the patients of PAH or combined pre-capillary and post-capillary PH (CpcPH) improved the hemodynamic parameters and increased 6MWD. Sympathetic overactivity aggravates PAH. PADN is a promising interventional treatment for PAH and CpcPH. Additional clinical trials are warranted to confirm the efficacy of PADN.
Topics: Denervation; Hemodynamics; Humans; Hypertension, Pulmonary; Pressoreceptors; Pulmonary Arterial Hypertension; Pulmonary Artery; Sympathectomy; Sympathetic Nervous System; Treatment Outcome
PubMed: 31486924
DOI: 10.1007/s11886-019-1203-z -
Nutrients Feb 2022For normal maintenance of blood pressure and blood volume a well-balanced renin-angiotensin-aldosterone system (RAS) is necessary. For this purpose, renin is secreted as... (Review)
Review
For normal maintenance of blood pressure and blood volume a well-balanced renin-angiotensin-aldosterone system (RAS) is necessary. For this purpose, renin is secreted as the situation demands by the juxtaglomerular cells (also called as granular cells) that are in the walls of the afferent arterioles. Juxtaglomerular cells can sense minute changes in the blood pressure and blood volume and accordingly synthesize, store, and secrete appropriate amounts of renin. Thus, when the blood pressure and blood volume are decreased JGA cells synthesize and secrete higher amounts of renin and when the blood pressure and blood volume is increased the synthesis and secretion of renin is decreased such that homeostasis is restored. To decipher this important function, JGA cells (renin cells) need to sense and transmit the extracellular physical forces to their chromatin to control renin gene expression for appropriate renin synthesis. The changes in perfusion pressure are sensed by Integrin β1 that is transmitted to the renin cell's nucleus via lamin A/C that produces changes in the architecture of the chromatin. This results in an alteration (either increase or decrease) in renin gene expression. Cell membrane is situated in an unique location since all stimuli need to be transmitted to the cell nucleus and messages from the DNA to the cell external environment can be conveyed only through it. This implies that cell membrane structure and integrity is essential for all cellular functions. Cell membrane is composed to proteins and lipids. The lipid components of the cell membrane regulate its (cell membrane) fluidity and the way the messages are transmitted between the cell and its environment. Of all the lipids present in the membrane, arachidonic acid (AA) forms an important constituent. In response to pressure and other stimuli, cellular and nuclear shape changes occur that render nucleus to act as an elastic mechanotransducer that produces not only changes in cell shape but also in its dynamic behavior. Cell shape changes in response to external pressure(s) result(s) in the activation of cPLA2 (cytosolic phospholipase 2)-AA pathway that stretches to recruit myosin II which produces actin-myosin cytoskeleton contractility. Released AA can undergo peroxidation and peroxidized AA binds to DNA to regulate the expression of several genes. Alterations in the perfusion pressure in the afferent arterioles produces parallel changes in the renin cell membrane leading to changes in renin release. AA and its metabolic products regulate not only the release of renin but also changes in the vanilloid type 1 (TRPV1) expression in renal sensory nerves. Thus, AA and its metabolites function as intermediate/mediator molecules in transducing changes in perfusion and mechanical pressures that involves nuclear mechanotransduction mechanism. This mechanotransducer function of AA has relevance to the synthesis and release of insulin, neurotransmitters, and other soluble mediators release by specialized and non-specialized cells. Thus, AA plays a critical role in diseases such as diabetes mellitus, hypertension, atherosclerosis, coronary heart disease, sepsis, lupus, rheumatoid arthritis, and cancer.
Topics: Arachidonic Acid; Juxtaglomerular Apparatus; Mechanotransduction, Cellular; Pressoreceptors; Renin
PubMed: 35215399
DOI: 10.3390/nu14040749 -
Autonomic Neuroscience : Basic &... Nov 2019Autonomic nervous system (ANS) has been extensively explored in obstructive sleep apnea (OSA). Autonomic alterations in these patients have been described by means of... (Review)
Review
Autonomic nervous system (ANS) has been extensively explored in obstructive sleep apnea (OSA). Autonomic alterations in these patients have been described by means of several methods, evaluating ANS function both directly with microneurography and indirectly through baroreflex sensitivity (BRS, by the sequence method or the cross-spectral approach), heart rate variability analysis (HRV, both in the time and frequency domain) during sleep and wake, or conventional laboratory tests, including cold pressor test, hand grip test or measurement of urinary cathecolamine excretion. Several studies in OSA patients have shown ANS alterations, in particular sympathetic overactivity, both acutely during apnea events and chronically during the daytime, being both also involved in cardiovascular consequences of sleep disordered breathing. The association between OSA and sympathetic dysregulation suggests a dose response relationship between OSA severity and the degree of sympathetic overactivity and this association seems to be reversible as the treatment of OSA is implemented. Additionally ANS is involved in regulating visceral and humoral functions to maintain the body homeostasis and in reaction and adaptation to external and internal stressor stimuli. However, the vast majority of studies have focussed on cardiovascular alterations, which are easier to measure, somewhat neglecting the other functions regulated by ANS. More evidence is therefore needed to better characterize the impact that sleep disorder breathing may have on ANS both in the short and long term.
Topics: Adaptation, Physiological; Autonomic Nervous System; Autonomic Nervous System Diseases; Baroreflex; Cardiovascular Diseases; Catecholamines; Continuous Positive Airway Pressure; Female; Gastrointestinal Diseases; Heart Rate; Humans; Male; Polysomnography; Pressoreceptors; Reflex, Abnormal; Sexual Dysfunction, Physiological; Sleep Apnea, Obstructive; Sleepiness; Urination Disorders
PubMed: 31445406
DOI: 10.1016/j.autneu.2019.102563 -
Trends in Cognitive Sciences Jan 2016Mental processes depend upon a dynamic integration of brain and body. Emotions encompass internal physiological changes which, through interoception (sensing bodily... (Review)
Review
Mental processes depend upon a dynamic integration of brain and body. Emotions encompass internal physiological changes which, through interoception (sensing bodily states), underpin emotional feelings, for example, cardiovascular arousal can intensify feelings of fear and anxiety. The brain is informed about how quickly and strongly the heart is beating by signals from arterial baroreceptors. These fire in bursts after each heartbeat, and are quiet between heartbeats. The processing of fear stimuli is selectively enhanced by these phasic signals, and these inhibit the processing of other types of stimuli including physical pain. Behavioural and neuroimaging studies detail this differential impact of heart signals on the processing of salient stimuli, and add to knowledge linking rhythmic activity in brain and body to perceptual consciousness.
Topics: Brain; Fear; Heart; Humans; Pressoreceptors
PubMed: 26628111
DOI: 10.1016/j.tics.2015.10.005 -
American Journal of Hypertension Dec 2016Hypertension (HTN) is a worldwide epidemic. When untreated, HTN places patients at an elevated risk for several health conditions, including cardiovascular disease and... (Review)
Review
Hypertension (HTN) is a worldwide epidemic. When untreated, HTN places patients at an elevated risk for several health conditions, including cardiovascular disease and end-organ damage. This effect is particularly pronounced in a subset of patients who experience treatment-resistant HTN despite the utilization of conventional medication and lifestyle interventions. For these challenging patients, ongoing research efforts continue to explore and develop novel nonpharmacologic therapies for resistant HTN. One such avenue is the regulation of the sympathetic nervous system, a large component of circulatory physiology. Innovative therapies have evolved to harness the ability to deliver electrical stimulation to baroreceptors in an effort to modulate the sympathetic system involvement in HTN. This review discusses baroreflex activation therapy and its role in the management of resistant HTN.
Topics: Antihypertensive Agents; Baroreflex; Blood Pressure; Clinical Trials as Topic; Drug Resistance; Electric Stimulation Therapy; Humans; Hypertension; Implantable Neurostimulators; Pressoreceptors; Prosthesis Design; Treatment Outcome
PubMed: 27444637
DOI: 10.1093/ajh/hpw074 -
Trends in Cardiovascular Medicine Nov 2016Treatment-resistant hypertension (TRH) is defined as elevated blood pressure despite treatment with three properly dosed antihypertensive drugs, and is associated with... (Review)
Review
Treatment-resistant hypertension (TRH) is defined as elevated blood pressure despite treatment with three properly dosed antihypertensive drugs, and is associated with adverse cardiovascular and renal outcomes and increased mortality. Treatment of patients with TRH focuses on maximizing the doses of antihypertensive drugs and adding drugs with complementary mechanisms of action, including a combination of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, calcium channel blockers, and thiazide-like diuretics. Randomized clinical trials have demonstrated the efficacy of the mineralocorticoid receptor antagonist spironolactone as a fourth-line therapy for patients with TRH. Other pharmacologic considerations include adding α-blockers, combined α-β-blockers, centrally acting α-agonists, or direct vasodilators. However, a small, but important subset of patients remain hypertensive despite combination regimens with multiple antihypertensive drugs, underscoring the need for novel blood pressure-lowering therapies. Over recent years, alternative approaches for treating TRH have emerged, including agonists of natriuretic peptides, endothelin-receptor antagonists, and additional vasoactive drugs. Lastly, device-based interventions, such as renal denervation or carotid baroreflex activation, may supplement drug therapy for these patients. This review summarizes current knowledge on the management of TRH, with focus on novel therapeutic strategies designed to achieve optimal blood pressure control.
Topics: Antihypertensive Agents; Baroreflex; Blood Pressure; Catheter Ablation; Drug Resistance; Drug Therapy, Combination; Electric Stimulation Therapy; Humans; Hypertension; Kidney; Pressoreceptors; Renal Artery; Sympathectomy; Treatment Outcome
PubMed: 27381561
DOI: 10.1016/j.tcm.2016.05.004 -
Circulation Research Mar 2015Hypertension is the most common modifiable risk factor for cardiovascular disease and death, and lowering blood pressure with antihypertensive drugs reduces target organ... (Review)
Review
Hypertension is the most common modifiable risk factor for cardiovascular disease and death, and lowering blood pressure with antihypertensive drugs reduces target organ damage and prevents cardiovascular disease outcomes. Despite a plethora of available treatment options, a substantial portion of the hypertensive population has uncontrolled blood pressure. The unmet need of controlling blood pressure in this population may be addressed, in part, by developing new drugs and devices/procedures to treat hypertension and its comorbidities. In this Compendium Review, we discuss new drugs and interventional treatments that are undergoing preclinical or clinical testing for hypertension treatment. New drug classes, eg, inhibitors of vasopeptidases, aldosterone synthase and soluble epoxide hydrolase, agonists of natriuretic peptide A and vasoactive intestinal peptide receptor 2, and a novel mineralocorticoid receptor antagonist are in phase II/III of development, while inhibitors of aminopeptidase A, dopamine β-hydroxylase, and the intestinal Na(+)/H(+) exchanger 3, agonists of components of the angiotensin-converting enzyme 2/angiotensin(1-7)/Mas receptor axis and vaccines directed toward angiotensin II and its type 1 receptor are in phase I or preclinical development. The two main interventional approaches, transcatheter renal denervation and baroreflex activation therapy, are used in clinical practice for severe treatment resistant hypertension in some countries. Renal denervation is also being evaluated for treatment of various comorbidities, eg, chronic heart failure, cardiac arrhythmias and chronic renal failure. Novel interventional approaches in early development include carotid body ablation and arteriovenous fistula placement. Importantly, none of these novel drug or device treatments has been shown to prevent cardiovascular disease outcomes or death in hypertensive patients.
Topics: Animals; Antihypertensive Agents; Arteriovenous Shunt, Surgical; Baroreflex; Carotid Body; Clinical Trials as Topic; Comorbidity; Decompression, Surgical; Drug Design; Drugs, Investigational; Electric Stimulation Therapy; Enzyme Inhibitors; Female; High-Intensity Focused Ultrasound Ablation; Humans; Hypertension; Ion Channels; Kidney; Kidney Tubules; Mineralocorticoid Receptor Antagonists; Models, Animal; Molecular Targeted Therapy; Multicenter Studies as Topic; Oxidative Stress; Pre-Eclampsia; Pregnancy; Pressoreceptors; Randomized Controlled Trials as Topic; Receptors, Cell Surface; Renal Artery; Renin-Angiotensin System; Stents; Sympathectomy; Sympathetic Nervous System; Therapies, Investigational
PubMed: 25767291
DOI: 10.1161/CIRCRESAHA.116.303603 -
Respiratory Physiology & Neurobiology Sep 2022Cough, the main airway defensive process, is modulated by multiple sensory inputs from the respiratory system and outside of it. This modulation is one of the mechanisms... (Review)
Review
Cough, the main airway defensive process, is modulated by multiple sensory inputs from the respiratory system and outside of it. This modulation is one of the mechanisms that contributes to the sensitization of cough pathways at the peripheral and/or central level via neuroplasticity and it manifests most often as augmented coughing. Cardiorespiratory coupling is an important mechanism responsible for a match between oxygenation and cardiac output and bidirectional relationships exist between respiration and cardiovascular function. While the impact of cough with the robust swings of the intrathoracic pressure on haemodynamic parameters and heart electrophysiology are well characterized, little is known about the modulation of cough by haemodynamic parameters - mainly the blood pressure. Some circumstantial findings from older animal studies and more recent sophisticated analysis confirm that baroreceptor stimulation and unloading alters coughing evoked in experiments. Clinical relevance of such findings is not presently known.
Topics: Animals; Baroreflex; Blood Pressure; Cardiac Output; Cough; Heart Rate; Pressoreceptors; Respiration
PubMed: 35595217
DOI: 10.1016/j.resp.2022.103921 -
Hypertension (Dallas, Tex. : 1979) May 2023
Topics: Humans; Baroreflex; COVID-19; Pressoreceptors; Sympathetic Nervous System; Blood Pressure; Afferent Pathways
PubMed: 36802914
DOI: 10.1161/HYPERTENSIONAHA.123.20316 -
Anesthesiology Apr 2019Baroreceptors are mechanosensitive elements of the peripheral nervous system that maintain homeostasis by coordinating physiologic responses to external and internal... (Review)
Review
Baroreceptors are mechanosensitive elements of the peripheral nervous system that maintain homeostasis by coordinating physiologic responses to external and internal stimuli. While it is recognized that carotid and cardiopulmonary baroreceptor reflexes modulate autonomic output to mitigate excessive fluctuations in arterial blood pressure and to maintain intravascular volume, increasing evidence suggests that baroreflex pathways also project to key regions of the central nervous system that regulate somatosensory, somatomotor, and central nervous system arousal. In addition to maintaining autonomic homeostasis, baroreceptor activity modulates the perception of pain, as well as neuroimmune, neuroendocrine, and cognitive responses to physical and psychologic stressors. This review summarizes the role that baroreceptor pathways play in modulating acute and chronic pain perception. The contribution of baroreceptor function to postoperative outcomes is also presented. Finally, methods that enhance baroreceptor function, which hold promise in improving postoperative and pain management outcomes, are presented.
Topics: Animals; Baroreflex; Humans; Pain; Pain Perception; Postoperative Complications; Pressoreceptors; Treatment Outcome
PubMed: 30418212
DOI: 10.1097/ALN.0000000000002510