Search

STUDY OBJECTIVE: African Americans (AAs) show early signs of vascular dysfunction paired with elevated blood pressure (BP) and total peripheral resistance (TPR), which is thought to underlie their increased rates of cardiovascular health complications relative to European Americans (EAs). AAs paradoxically have higher cardiac vagal tone, indexed by heart rate variability (HRV), which is cardio-protective. This paradox has been termed the Cardiovascular Conundrum. The physiological mechanism underlying this phenomenon is not well understood. We examined race differences in baroreflex function, which might be an important mechanism underlying the Cardiovascular Conundrum. DESIGN: Participants completed a 5-minute baseline period where resting cardiac metrics were assessed. SETTING: Laboratory. PARTICIPANTS: 130 college-aged individuals (54 women, 57 AAs). MAIN OUTCOME MEASURES: Baroreflex function was indexed as baroreflex sensitivity (BRS; the magnitude of changes in cardiovascular activity in accordance with BP changes) and effectiveness (BEI; the ratio of BP changes that elicit changes in cardiovascular activity) in the cardiac, vascular, and myocardial limbs. RESULTS AND CONCLUSIONS: Results showed AAs to have higher HRV and cardiac BRS in comparison to EAs, suggesting the baroreflex is more sensitive to correcting the heart period for changes in BP among AAs compared to EAs. However, AAs showed lower vascular BEI relative to EAs, suggesting less effective control of TPR. In sum, lower BEI in the vascular branch might be an important mechanism underlying the Cardiovascular Conundrum (i.e., higher HRV and BP) and by extension, health disparities in cardiovascular diseases between AAs and EAs.

The autonomic regulation of the pulmonary vasculature has been under‐appreciated despite the presence of sympathetic and parasympathetic neural innervation and adrenergic and cholinergic receptors on pulmonary vessels. Recent clinical trials targeting this innervation have demonstrated promising effects in pulmonary hypertension, and in this context of reignited interest, we review autonomic pulmonary vascular regulation, its integration with other pulmonary vascular regulatory mechanisms, systemic homeostatic reflexes and their clinical relevance in pulmonary hypertension. The sympathetic and parasympathetic nervous systems can affect pulmonary vascular tone and pulmonary vascular stiffness. Local afferents in the pulmonary vasculature are activated by elevations in pressure and distension and lead to distinct pulmonary baroreflex responses, including pulmonary vasoconstriction, increased sympathetic outflow, systemic vasoconstriction and increased respiratory drive. Autonomic pulmonary vascular control interacts with, and potentially makes a functional contribution to, systemic homeostatic reflexes, such as the arterial baroreflex. New experimental therapeutic applications, including pulmonary artery denervation, pharmacological cholinergic potentiation, vagal nerve stimulation and carotid baroreflex stimulation, have shown some promise in the treatment of pulmonary hypertension. What is the topic of this review?This review examines our understanding of the autonomic control of pulmonary circulation, with an emphasis on its clinical relevance and potential therapeutic targeting in pulmonary hypertension.What advances does it highlight?The sympathetic and parasympathetic nervous systems both regulate pulmonary vascular tone and stiffness, in integration with systemic autonomic homeostasis. Pulmonary vascular afferents responsive to pulmonary arterial pressure produce distinct pulmonary baroreflex responses. Dysfunction in autonomic control both to and from the pulmonary vasculature might contribute to pulmonary hypertension, and new approaches targeting this have demonstrated early success. [ABSTRACT FROM AUTHOR]

The first act of life was the capture of water within a cell membrane, 1 and maintaining fluid homeostasis is critical for the survival of most organisms. In this review, we discuss the neural mechanisms that drive animals to seek out and consume water and salt. We discuss the cellular and molecular mechanisms for sensing imbalances in blood osmolality, volume, and sodium content; how this information is integrated in the brain to produce thirst and salt appetite; and how these motivational drives are rapidly quenched by the ingestion of water and salt. We also highlight some of the gaps in our current understanding of the fluid homeostasis system, including the molecular identity of the key sensors that detect many fluid imbalances, as well as the mechanisms that control drinking in the absence of physiologic deficit, such as during meals. Thirst and salt appetite are critical for maintaining fluid balance. In this review, Grove and Knight discuss how fluid imbalances are sensed at a molecular level and how these signals converge on brain circuits to drive water and salt consumption. [ABSTRACT FROM AUTHOR]

Key points Microneurographic recordings of the human cervical vagus nerve have revealed the presence of multi‐unit neural activity with measurable cardiac rhythmicity. This suggests that the physiology of vagal neurones with cardiovascular regulatory function can be studied using this method. Here, the activity of cardiac rhythmic single units was discriminated from human cervical vagus nerve recordings using template‐based waveform matching. The activity of 44 cardiac rhythmic neurones (22 with myelinated axons and 22 with unmyelinated axons) was isolated. By consideration of each unit's firing pattern with respect to the cardiac and respiratory cycles, the functional identification of each unit was attempted. Of note is the observation of seven cardiac rhythmic neurones with myelinated axons whose activity was recruited or enhanced by slow, deep breathing, was maximal during the nadir of respiratory sinus arrhythmia, and showed an expiratory peak. This is characteristic of cardioinhibitory efferent neurones, which are responsible for respiratory sinus arrhythmia. The remaining 15 cardiac rhythmic neurones with myelinated axons were categorised as cardiopulmonary receptors or arterial baroreceptors based on the position of their peak in firing with respect to the R‐wave of the cardiac cycle. This latter method is not viable for neurones with unmyelinated axons due to their slow and unknown conduction velocities. With the exception of three neurones whose expiratory modulation implicates them as cardiac‐projecting efferent neurones, this population is likely dominated by arterial baroreceptors. In conclusion, the activity of single units with cardiovascular function has been discriminated within the human cervical vagus, enabling their systematic study. Recordings of the electrical activity of the vagus nerve have recently been made at the level of the neck in humans. Examination of the gross activity of this nerve reveals subpopulations of neurones whose activity fluctuates in time with the heart's beat, suggesting that the neurones that monitor or modify cardiac function can be studied using this method. Here, the activity of individual cardiac rhythmic neurones was isolated from human vagus nerve recordings using template‐based spike sorting. The relationship between this activity and the cardiac and respiratory cycles was used as a means of classifying each neurone. Neuronal firing patterns that are consistent with that of neurones that modify cardiac function, including heart‐slowing ‘cardioinhibitory’ neurones, as well as neurones that inform the brain of cardiovascular status were observed. This approach enables, for the first time, the systematic study of the function of these neurones in humans in both health and disease. [ABSTRACT FROM AUTHOR]

The flower‐spray nerve endings are afferent nerve terminals in the carotid sinus that arise from carotid sinus nerve of glossopharyngeal nerve. However, the three‐dimensional ultrastructural characteristics of flower‐spray nerve endings and spatial relationships between the terminal parts and other cellular elements have not been fully understood. To elucidate their detailed relationship, backscattered electron imaging of serial sections was performed with a scanning electron microscope to produce a three‐dimensional reconstruction of the flower‐spray endings. The terminal parts of flower‐spray endings were distributed horizontally approximately 5 µm outside the external elastic membrane in the tunica adventitia of the internal carotid artery. The three‐dimensional reconstruction showed that the terminal parts of flower‐spray endings were flat with irregular contours and were partially covered by the thin cytoplasmic processes of Schwann cells. The complex consisting of the nerve terminals and associated Schwann cells was surrounded by a multilayered basement membrane. The terminal parts of the endings were also surrounded by fibroblasts with elastic fibers and collagen fibrils. Secretory vesicles without an electron‐dense core were observed in the terminal parts of the endings. The accumulation of vesicles just below the axonal membrane was observed in terminal parts not covered by Schwann cell cytoplasmic processes on both the luminal and basal sides. Swollen mitochondria, concentric membranous structures, and glycogen granule‐like electron‐dense materials were often noted in some of the terminal parts of the endings and the parent axon. Collectively, the present results suggest that flower‐spray endings are baroreceptors because their morphology was similar to other mechanoreceptors. Furthermore, flower‐spray endings may be affected by glutamate secreted in an autocrine manner. [ABSTRACT FROM AUTHOR]

Cardiovascular homeostasis is maintained, in part, by neural signals arising from arterial baroreceptors that apprise the brain of blood volume and pressure. Here, we test whether neurons within the nodose ganglia that express angiotensin type-1a receptors (referred to as NGAT1aR) serve as baroreceptors that differentially influence blood pressure (BP) in male and female mice. Using Agtr1a-Cre mice and Cre-dependent AAVs to direct tdTomato to NGAT1aR, neuroanatomical studies revealed that NGAT1aR receive input from the aortic arch, project to the caudal nucleus of the solitary tract (NTS), and synthesize mechanosensitive ion channels, Piezo1/2. To evaluate the functionality of NGAT1aR, we directed the fluorescent calcium indicator (GCaMP6s) or the light-sensitive channelrhodopsin-2 (ChR2) to Agtr1a-containing neurons. Two-photon intravital imaging in Agtr1a-GCaMP6s mice revealed that NGAT1aR couple their firing to elevated BP, induced by phenylephrine (i.v.). Furthermore, optical excitation of NGAT1aR at their soma or axon terminals within the caudal NTS of Agtr1a-ChR2 mice elicited robust frequency-dependent decreases in BP and heart rate, indicating that NGAT1aR are sufficient to elicit appropriate compensatory responses to vascular mechanosensation. Optical excitation also elicited hypotensive and bradycardic responses in ChR2-expressing mice that were subjected to deoxycorticosterone acetate (DOCA)-salt hypertension; however, the duration of these effects was altered, suggestive of hypertension-induced impairment of the baroreflex. Similarly, increased GCaMP6s fluorescence observed after administration of phenylephrine was delayed in mice subjected to DOCA-salt or chronic delivery of angiotensin II. Collectively, these results reveal the structure and function of NGAT1aR and suggest that such neurons may be exploited to discern and relieve hypertension. [ABSTRACT FROM AUTHOR]

Study objective: African Americans (AAs) show early signs of vascular dysfunction paired with elevated blood pressure (BP) and total peripheral resistance (TPR), which is thought to underlie their increased rates of cardiovascular health complications relative to European Americans (EAs). AAs paradoxically have higher cardiac vagal tone, indexed by heart rate variability (HRV), which is cardio-protective. This paradox has been termed the Cardiovascular Conundrum. The physiological mechanism underlying this phenomenon is not well understood. We examined race differences in baroreflex function, which might be an important mechanism underlying the Cardiovascular Conundrum. Design: Participants completed a 5-minute baseline period where resting cardiac metrics were assessed. Setting: Laboratory. Participants: 130 college-aged individuals (54 women, 57 AAs). Main outcome measures: Baroreflex function was indexed as baroreflex sensitivity (BRS; the magnitude of changes in cardiovascular activity in accordance with BP changes) and effectiveness (BEI; the ratio of BP changes that elicit changes in cardiovascular activity) in the cardiac, vascular, and myocardial limbs. Results and conclusions: Results showed AAs to have higher HRV and cardiac BRS in comparison to EAs, suggesting the baroreflex is more sensitive to correcting the heart period for changes in BP among AAs compared to EAs. However, AAs showed lower vascular BEI relative to EAs, suggesting less effective control of TPR. In sum, lower BEI in the vascular branch might be an important mechanism underlying the Cardiovascular Conundrum (i.e., higher HRV and BP) and by extension, health disparities in cardiovascular diseases between AAs and EAs.

Background/objective: Blood donation is considered to be a safe procedure, however, sometimes vasovagal reactions (VVRs) with various degrees of severity can occur. This paper provides an overview of the incidence of VVR with a focus on vasovagal syncope (VVS, temporary loss of consciousness), risk factors, and possible consequences of VVR/VVS for donors, as well as effects of interventions that are used to reduce VVR/VVS among blood donors. We also discuss mechanisms underlying VVS and evolutionary explanations for VVS. Methods: Relevant studies were found by search in PubMed. Results: Reported incidence of VVS varies from 0.1% to 0.5%, with higher incidence among younger and first-time donors, but mixed results have been found for gender differences: whereas some studies report higher incidence among female donors, other studies find no differences. Anxiety, fear of needles or seeing blood are frequent triggers of VVR/VVS, particularly among first-time donors. Donors who have experienced VVR/VVS are less likely to return to donate. Physiologic interventions such as pre-donation water intake and applied muscle tension during donation, alone or in combination, have shown effect in reducing VVR/VVS in several studies. Psychological interventions such as distraction and social support have also shown to reduce the risk of VVR/VVS. From an evolutionary perspective, VVS may have had a survival advantage in the distant past.

BackgroundPosttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) share overlapping symptom presentations and are highly comorbid conditions among Veteran populations. Despite elevated presentations of PTSD after mTBI, mechanisms linking the two are unclear, although both have been associated with alterations in white matter and disruptions in autonomic regulation. The present study aimed to determine if there is regional variability in white matter correlates of symptom severity and autonomic functioning in a mixed sample of Veterans with and without PTSD and/or mTBI (N = 77).MethodsDiffusion-weighted images were processed to extract fractional anisotropy (FA) values for major white matter structures. The PTSD Checklist-Military version (PCL-M) and Neurobehavioral Symptom Inventory (NSI) were used to determine symptom domains within PTSD and mTBI. Autonomic function was assessed using continuous blood pressure and respiratory sinus arrythmia during a static, standing angle positional test. Mixed-effect models were used to assess the regional specificity of associations between symptom severity and white matter, with FA, global symptom severity (score), and white matter tract (tract) as predictors. Additional interaction terms of symptom domain (i.e., NSI and PCL-M subscales) and loss of consciousness (LoC) were added to evaluate potential moderating effects. A parallel analysis was conducted to explore concordance with autonomic functioning.ResultsResults from the two-way Score × Tract interaction suggested that global symptom severity was associated with FA in the cingulum angular bundle (positive) and uncinate fasciculus (negative) only, without variability by symptom domain. We also found regional specificity in the relationship between FA and autonomic function, such that FA was positively associated with autonomic function in all tracts except the cingulum angular bundle. History of LoC moderated the association for both global symptom severity and autonomic function.ConclusionsOur findings are consistent with previous literature suggesting that there is significant overlap in the symptom presentation in TBI and PTSD, and white matter variability associated with LoC in mTBI may be associated with increased PTSD-spectra symptoms. Further research on treatment response in patients with both mTBI history and PTSD incorporating imaging and autonomic assessment may be valuable in understanding the role of brain injury in treatment outcomes and inform treatment design.

Abstract Aims Baroreflex activation therapy (BAT) is an innovative treatment option for advanced heart failure (HFrEF). We analysed patients' BAT acceptance and the outcome of BAT patients compared with HFrEF patients solely treated with a guideline‐directed medical therapy (GDMT) and studied effects of sacubitril/valsartan (ARNI). Methods In this prospective study, 40 HFrEF patients (71 ± 3 years, 20% female) answered a questionnaire on the acceptance of BAT. Follow‐up visits were performed after 3, 6, and 12 months. Primary efficacy endpoints included an improvement in QoL, NYHA class, LVEF, HF hospitalization, NT‐proBNP levels, and 6MHWD. Results Twenty‐nine patients (73%) showed interest in BAT. Ten patients (25%) opted for implantation. BAT and BAT + ARNI patients developed an increase in LVEF (BAT +10%, P‐value (P) = 0.005*; BAT + ARNI +9%, P = 0.049*), an improved NYHA class (BAT −88%, P = 0.014*, BAT + ARNI −90%, P = 0.037*), QoL (BAT +21%, P = 0.020*, BAT + ARNI +22%, P = 0.012*), and reduced NT‐proBNP levels (BAT −24%, P = 0.297, BAT + ARNI −37%, P = 0.297). BAT HF hospitalization rates were lower (50%) compared with control group patients (83%) (P = 0.020*). Conclusions Although BAT has generated considerable interest, acceptance appears to be ambivalent. BAT improves outcome with regard to LVEF, NYHA class, QoL, NT‐proBNP levels, and HF hospitalization rates. BAT + ARNI resulted in more pronounced effects than ARNI alone.

Acid Sensing Ion Channels (ASIC) are proton sensors involved in several physiological and pathophysiological functions including synaptic plasticity, sensory systems and nociception. ASIC channels have been ubiquitously localized in neurons and play a role in their excitability. Information about ASIC channels in cardiomyocyte function is limited. Evidence indicates that ASIC subunits are expressed in both, plasma membrane and intracellular compartments of mammalian cardiomyocytes, suggesting unrevealing functions in the cardiomyocyte physiology. ASIC channels are expressed in neurons of the peripheral nervous system including the nodose and dorsal root ganglia (DRG), both innervating the heart, where they play a dual role as mechanosensors and chemosensors. In baroreceptor neurons from nodose ganglia, mechanosensation is directly associated with ASIC2a channels for detection of changes in arterial pressure. ASIC channels expressed in DRG neurons have several roles in the cardiovascular function. First, ASIC2a/3 channel has been proposed as the molecular sensor of cardiac ischemic pain for its pH range activation, kinetics and the sustained current. Second, ASIC1a seems to have a critical role in ischemia-induced injury. And third, ASIC1a, 2 and 3 are part of the metabolic component of the exercise pressure reflex (EPR). This review consists of a summary of several reports about the role of ASIC channels in the cardiovascular system and its innervation. [ABSTRACT FROM AUTHOR]

Acid Sensing Ion Channels (ASIC) are proton sensors involved in several physiological and pathophysiological functions including synaptic plasticity, sensory systems and nociception. ASIC channels have been ubiquitously localized in neurons and play a role in their excitability. Information about ASIC channels in cardiomyocyte function is limited. Evidence indicates that ASIC subunits are expressed in both, plasma membrane and intracellular compartments of mammalian cardiomyocytes, suggesting unrevealing functions in the cardiomyocyte physiology. ASIC channels are expressed in neurons of the peripheral nervous system including the nodose and dorsal root ganglia (DRG), both innervating the heart, where they play a dual role as mechanosensors and chemosensors. In baroreceptor neurons from nodose ganglia, mechanosensation is directly associated with ASIC2a channels for detection of changes in arterial pressure. ASIC channels expressed in DRG neurons have several roles in the cardiovascular function. First, ASIC2a/3 channel has been proposed as the molecular sensor of cardiac ischemic pain for its pH range activation, kinetics and the sustained current. Second, ASIC1a seems to have a critical role in ischemia-induced injury. And third, ASIC1a, 2 and 3 are part of the metabolic component of the exercise pressure reflex (EPR). This review consists of a summary of several reports about the role of ASIC channels in the cardiovascular system and its innervation.

Hyponatremia is frequently found in patients with congestive heart failure. A reduction in effective circulatory blood volume in a volume-expanded patient with decreased cardiac output is linked to a baroreceptor-mediated non-osmotic release of arginine vasopressin (AVP). The increased production of AVP and salt and water retention in the proximal and distal tubules of the kidney by humoral, hemodynamic, and neural mechanisms increase circulatory blood volume and contribute to hyponatremia. Recent studies have indicated that hyponatremia predicts the short-term and long-term prognosis of heart failure by increasing cardiac death and rehospitalization. In addition, the early development of hyponatremia in acute myocardial infarction also predicts the long-term prognosis of worsening heart failure. AVP V2 receptor antagonism may relieve water retention, but it is unknown whether the V2 receptor inhibitor, tolvaptan, improves the long-term prognosis of congestive heart failure. The newly identified natriuretic factor in renal salt wasting has the potential of improving clinical outcomes when combined with a distal diuretic. [ABSTRACT FROM AUTHOR]

Aims: Baroreflex activation therapy (BAT) is an innovative treatment option for advanced heart failure (HFrEF). We analysed patients' BAT acceptance and the outcome of BAT patients compared with HFrEF patients solely treated with a guideline‐directed medical therapy (GDMT) and studied effects of sacubitril/valsartan (ARNI). Methods: In this prospective study, 40 HFrEF patients (71 ± 3 years, 20% female) answered a questionnaire on the acceptance of BAT. Follow‐up visits were performed after 3, 6, and 12 months. Primary efficacy endpoints included an improvement in QoL, NYHA class, LVEF, HF hospitalization, NT‐proBNP levels, and 6MHWD. Results: Twenty‐nine patients (73%) showed interest in BAT. Ten patients (25%) opted for implantation. BAT and BAT + ARNI patients developed an increase in LVEF (BAT +10%, P‐value (P) = 0.005*; BAT + ARNI +9%, P = 0.049*), an improved NYHA class (BAT −88%, P = 0.014*, BAT + ARNI −90%, P = 0.037*), QoL (BAT +21%, P = 0.020*, BAT + ARNI +22%, P = 0.012*), and reduced NT‐proBNP levels (BAT −24%, P = 0.297, BAT + ARNI −37%, P = 0.297). BAT HF hospitalization rates were lower (50%) compared with control group patients (83%) (P = 0.020*). Conclusions: Although BAT has generated considerable interest, acceptance appears to be ambivalent. BAT improves outcome with regard to LVEF, NYHA class, QoL, NT‐proBNP levels, and HF hospitalization rates. BAT + ARNI resulted in more pronounced effects than ARNI alone. [ABSTRACT FROM AUTHOR]

Multiple sensor theory (MST) has advanced our understanding of how lung mechanosensors operate. That is, single lung units contain multiple homogeneous or heterogeneous sensors. Each detects sensor-specific mechanical information and interacts with other sensors lying within the unit sending integrated information to the brain to evoke reflexes. MST explains numerous controversial issues in the respiratory system. Recent studies in baroreceptors (BRs), along with reinterpretation of recordings appearing in the literature, indicate MST also operates in the cardiovascular (CV) system. This review outlines evidence supporting MST in the CV system and provides examples to apply the theory. Longstanding controversies surrounding the CV sensors are also considered. [ABSTRACT FROM AUTHOR]

Renin-expressing juxtaglomerular (JG) cells possess an intrinsic pressure-sensing mechanism(s) that regulates renin synthesis and release in response to changes in perfusion pressure. Although we recently described the structure of the nuclear mechanotransducer that controls renin transcription, the acute pressure-sensing mechanism that controls the rapid release of renin has not been identified. In JG cells there is an inverse relationship between intracellular calcium and renin release, the 'calcium paradox'. Since the discovery of Piezo2 as the 'touch' receptors, there has been a significant interest in exploring whether they are also involved in other tissues beyond the skin. Given that Piezo receptors are permeable to calcium upon mechanical stimuli, it would be reasonable to hypothesize that Piezo2 controls renin synthesis and/or release in JG cells. To test this hypothesis, we used a variety of novel mouse models and JG cell-specific techniques to define whether Piezo2 controls renin expression and/or release in JG cells. Our in vivo data using constitutive and inducible Cre driver mouse lines and a variety of novel experimental approaches indicate that Piezo2 channels are not necessary for renin synthesis or release in JG cells during normal conditions or when homeostasis is threatened by hypotension, sodium depletion, or inverse changes in blood pressure. Furthermore, Piezo1 channels do not compensate for the lack of Piezo2 in JG cells. Efforts should be devoted to identifying the acute mechanosensory mechanisms controlling renin release., (© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

The mind is embodied, and this is relevant to mental health and psychiatric illness. Interoception is the body-to-brain axis of sensory information flow and its representation at the neural and psychological levels. Interoception is the purported basis for motivation and emotion, and as an inescapable stream of information about the health and functioning of the whole organism, it is proposed to be the foundation to the conscious unitary sense of self. Correspondingly, this central representation of internal state is relevant to understanding the expression of psychological symptoms and behaviours and ultimately psychiatric disorders. Here we review interoception, particularly from a cardiovascular perspective, and how understanding theoretical neural and psychological aspects of interoception relates to perceptions, thoughts, and feelings. We examine how perturbations in interoceptive processing are expressed in mental symptoms and psychiatric disorders and show how this knowledge may yield new treatment targets., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Multiple sensor theory (MST) has advanced our understanding of how lung mechanosensors operate. That is, single lung units contain multiple homogeneous or heterogeneous sensors. Each detects sensor-specific mechanical information and interacts with other sensors lying within the unit sending integrated information to the brain to evoke reflexes. MST explains numerous controversial issues in the respiratory system. Recent studies in baroreceptors (BRs), along with reinterpretation of recordings appearing in the literature, indicate MST also operates in the cardiovascular (CV) system. This review outlines evidence supporting MST in the CV system and provides examples to apply the theory. Longstanding controversies surrounding the CV sensors are also considered.

• Perceived increase in vascular stretch decreases salt intake after water deprivation. • NTS AT1R+ neurons and afferents may integrate sensory and endocrine input. • NTS AT1R+neurons and afferents regulate salt intake in water-deprived mice. Angiotensin-II (Ang-II) production is driven by deviations in blood volume and osmolality, and serves the role of regulating blood pressure and fluid intake to maintain cardiovascular and hydromineral homeostasis. These actions are mediated by Ang-II acting on its type 1a receptor (AT1aR) within the central nervous system and periphery. Of relevance, AT1aR are expressed on sensory afferents responsible for conveying cardiovascular information to the nucleus of the solitary tract (NTS). We have previously determined that optical excitation of neurons and vagal afferents within the NTS that express AT1aR (referred to as NTSAT1aR) mimics the perception of increased vascular stretch and induces compensatory responses to restore blood pressure. Here, we test whether NTSAT1aR are also involved in the modulation of water and sodium intake. We directed the light-sensitive excitatory channelrhodopsin-2 (ChR2) or inhibitory halorhodopsin (Halo) to Agtr1a -containing neurons and measured water and sodium chloride (NaCl) intake in the presence and absence of optical stimulation within the NTS during various challenges to fluid homeostasis. Optical perturbation of NTSAT1aR modulates NaCl intake, such that excitation attenuates, whereas inhibition increases intake. This effect is only observed in the water-deprived condition, suggesting that NTSAT1aR are involved in the regulation of sodium intake during an imbalance in both the intracellular and extracellular fluid compartments. Furthermore, optical excitation of NTSAT1aR increases c-Fos expression within oxytocinergic neurons of the paraventricular nucleus of the hypothalamus (PVN), indicating that the regulation of sodium intake by NTSAT1aR may be mediated by oxytocin. Collectively, these results reveal that NTSAT1aR are sufficient and necessary to modulate sodium intake relative to perceived changes in vascular stretch. [ABSTRACT FROM AUTHOR]

Maintaining an equilibrium between oxygen supply and demand is a principal function of the cardiovascular system. In times of altered metabolic demand, mechanisms exist to maintain the balance between supply and demand. Exercise, haemorrhage and pregnancy all lead to changes in oxygen demand and subsequently modification of cardiac output. During isotonic exercise, metabolic demands of muscle are greatly increased. Sympathetic stimulation and inhibition of the parasympathetic system lead to increases in heart rate and venous return, increasing cardiac output. This allows a proportional increase in blood flow to the exercising muscle. Cardiac output increases throughout pregnancy. In the first and second trimesters this rise is mainly due to an increase in stroke volume; however, during the later stages of pregnancy stroke volume reaches a plateau and further increase in cardiac output is mediated by a rising heart rate. In contrast, during haemorrhage, decreased venous return leads to a reduction in cardiac output, with a baroreceptor response due to the drop in arterial blood pressure. The tachycardia and vasoconstriction which follows are compensatory mechanisms in an attempt to preserve blood pressure. The Valsalva manoeuvre illustrates several aspects of reflex control of the cardiovascular system and allows non-invasive assessment and quantification of control mechanisms. Changes in stroke volume during the respiratory cycle can be used to predict fluid responsiveness and can be measured as pulse pressure variation or stroke volume variation. [ABSTRACT FROM AUTHOR]

The association between blood viscosity and pathological conditions involving a number of organ systems is well known. However, how the body measures and maintains appropriate blood viscosity is not well-described. The literature endorsing the function of the carotid sinus as a site of baroreception can be traced back to some of the earliest descriptions of digital pressure on the neck producing a drop in blood delivery to the brain. For the last 30 years, improved computational fluid dynamic (CFD) simulations of blood flow within the carotid sinus have demonstrated a more nuanced understanding of the changes in the region as it relates to changes in conventional metrics of cardiovascular function, including blood pressure. We suggest that the unique flow patterns within the carotid sinus may make it an ideal site to transduce flow data that can, in turn, enable real-time measurement of blood viscosity. The recent characterization of the PIEZO receptor family in the sinus vessel wall may provide a biological basis for this characterization. When coupled with other biomarkers of cardiovascular performance and descriptions of the blood rheology unique to the sinus region, this represents a novel venue for bioinspired design that may enable end-users to manipulate and optimize blood flow.

Background: Although it has been established that continuous flow left ventricular assist devices are sensitive to loading conditions, the effect of acute load and postural changes on pump flow have not been explored systematically.Methods and Results: Fifteen stable outpatients were studied. Patients sequentially transitioned from the seated position to supine, passive leg raise, and standing with transition effects documented. A modified Valsalva maneuver, consisting of a forced expiration with an open glottis, was performed in each position. A sustained, 2-handed handgrip was performed in the supine position. The pump flow waveform was recorded continuously and left ventricular end-diastolic diameter measured during each stage using transthoracic echocardiography. Transitioning from seated to supine posture produced a significant increase in the flow and the ventricular end-diastolic diameter, consistent with an increased preload. The transition from supine to standing produced a transient increase in the mean flow and decreased the flow pulsatility index. At steady state, these changes were reversed with a decrease in the mean and trough flow and increased pulsatility index, consistent with venous redistribution and possible baroreflex compensation. Four distinct patterns of standing-induced flow waveform effects were identified, reflecting varying preload, afterload, and individual compensatory effects. A sustained handgrip produced a significant decrease in flow and increase in flow pulsatility across all patients, reflecting an increased afterload pressure. A modified Valsalva maneuver produced a decrease in the flow pulsatility while seated, supine, and standing, but not during leg raise. Five patterns of pulsatility effect during Valsalva were observed: (1) minimal change, (2) pulsatility recovery, (3) rapid flatline, (4) slow flatline with delayed flow recovery, and (5) primary suction.Conclusions: Acute disturbances in loading conditions produce heterogeneous pump flow responses reflecting their complex interactions with pump and ventricular function as well as reflex compensatory mechanisms. Differences in responses and individual variabilities have significant implications for automated pump control algorithms. [ABSTRACT FROM AUTHOR]

A growing body of research suggests that perception and cognition are affected by fluctuating bodily states. For example, the rate of information sampling is coupled with cardiac phases. However, the benefits of such spontaneous coupling between bodily oscillations and decision-making remains unclear. Here, we studied the role of the cardiac cycle in information sampling by testing whether sequential information sampling phase-locked to systolic or diastolic parts of the cardiac cycle impacts the rate of information gathering and processing. To this aim, we employed a modified Information Sampling Task, a standard measure of the rate of information gathering before reaching a decision, in which the onset of new information delivery in each trial was coupled either to cardiac systole or diastole. Information presented within cardiac systole did not significantly modulate the information processing in a manner that would produce clear behavioral changes. However, we found evidence suggesting that higher interoceptive awareness increased accuracy, especially in the costly version of the task, when new information was sequentially presented at systole. Overall, our results add to a growing body of research on body-brain interactions and suggest that our internal bodily rhythms (i.e., heartbeats) and our awareness of them can interact with the way we process the noisy world around us. [Display omitted] • We developed a cardiac Information Sampling Task. • Information gathering in systole or diastole did not affect information gathering. • Higher interoceptive awareness increased accuracy in the costly version of the task. • This was particularly strong when new information was delivered at cardiac systole. [ABSTRACT FROM AUTHOR]

The most commonly used technique to study the barostatic regulation of blood pressure in ectothermic vertebrates consists of determining the heart rate response to pharmacological manipulations of blood pressure, the so‐called "Oxford method." Although well established, the Oxford method has some important limitations, such as induction of hypervolemia in small animals and undesired effects of vasoactive drugs on central and peripheral baroreflex components. As an alternative, the sequence method, which consists in the computerized evaluation of naturally‐occurring baroreflex adjustments of heart rate without the need for pharmacological administrations, was developed to study baroreflexes. In the present study, we compare this sequence method with the Oxford technique in two teleost species with different life styles, and we assess the optimal software configuration for the employment of the sequence method in fish. Calculation of baroreflex gain through the sequence method was adequate and reliable when the software was configured to search for baroreflex sequences with a minimum length of three cardiac cycles with a delay of one cardiac cycle between fluctuations in mean ventral aortic blood pressure and reflex changes in pulse interval. When properly configured, the sequence and the Oxford methods yielded similar determinations of the baroreflex gain in fish. Research Highlights: The nonpharmacological sequence method was validated to study the baroreflex function of fish.When properly configured, the sequence method yielded determinations of baroreflex gain similar to that of the Oxford method. [ABSTRACT FROM AUTHOR]

Mayer waves may synchronize overlapping propriobulbar interneuronal microcircuits constituting the respiratory rhythm and pattern generator, sympathetic oscillators, and cardiac vagal preganglionic neurons. Initially described by Sir Sigmund Mayer in the year 1876 in the arterial pressure waveform of anesthetized rabbits, authors have since extensively observed these oscillations in recordings of hemodynamic variables, including arterial pressure waveform, peripheral resistance, and blood flow. Authors would later reveal the presence of these oscillations in sympathetic neural efferent discharge and brainstem and spinal zones corresponding with sympathetic oscillators. Mayer wave central tendency proves highly consistent within, though the specific frequency band varies extensively across, species. Striking resemblance of the Mayer wave central tendency to the species-specific baroreflex resonant frequency has led the majority of investigators to comfortably presume, and generate computational models premised upon, a baroreflex origin of these oscillations. Empirical interrogation of this conjecture has generated variable results and derivative interpretations. Sinoaortic denervation and effector sympathectomy variably reduces or abolishes spectral power contained within the Mayer wave frequency band. Refractorines of Mayer wave generation to barodeafferentation lends credence to the hypothesis these waves are chiefly generated by brainstem propriobulbar and spinal cord propriospinal interneuronal microcircuit oscillators and likely modulated by the baroreflex. The presence of these waves in unitary discharge of medullary lateral tegmental field and rostral ventrolateral medullary neurons (contemporaneously exhibiting fast sympathetic rhythms [2–6 and 10 Hz bands]) in spectral variability in vagotomized pentobarbital-anesthetized and unanesthetized midcollicular (i.e., intercollicular) decerebrate cats supports genesis of Mayer waves by supraspinal sympathetic microcircuit oscillators. Persistence of these waves following high cervical transection in vagotomized unanesthetized midcollicular decerebrate cats would seem to suggest spinal sympathetic microcircuit oscillators generate these waves. The widespread presence of Mayer waves in brainstem sympathetic-related and non-sympathetic-related cells would seem to betray a general tendency of neurons to oscillate at this frequency. We have thus presented an extensive and, hopefully cohesive, discourse evaluating, and evolving the interpretive consideration of, evidence seeking to illumine our understanding of origins of, and insight into mechanisms contributing to, the genesis of Mayer waves. We have predicated our arguments and conjectures in the substance and matter of empirical data, though we have occasionally waxed philosophical beyond these traditional confines in suggesting interpretations exceeding these limits. We believe our synthesis and interpretation of the relevant literature will fruitfully inspire future studies from the perspective of a more intimate appreciation and conceptualization of network mechanisms generating oscillatory variability in neuronal and neural outputs. Our evaluation of Mayer waves informs a novel set of disciplines we term quantum neurophysics extendable to describing subatomic reality. Beyond informing our appreciation of mechanisms generating sympathetic oscillations, Mayer waves may constitute an intrinsic property of neurons extant throughout the cerebrum, brainstem, and spinal cord or reflect an emergent property of interactions between arteriogenic and neuronal oscillations.

This review describes and summarizes the role of neuronal nitric oxide synthase (nNOS) on the central nervous system, particularly on brain regions such as the ventrolateral medulla (VLM) and the periaqueductal gray matter (PAG), and on blood vessels and the heart that are involved in the regulation and control of the cardiovascular system (CVS). Furthermore, we shall also review the functional aspects of nNOS during several physiological, pathophysiological, and clinical conditions such as exercise, pain, cerebral vascular accidents or stroke and hypertension. For example, during stroke, a cascade of molecular, neurochemical, and cellular changes occur that affect the nervous system as elicited by generation of free radicals and nitric oxide (NO) from vulnerable neurons, peroxide formation, superoxides, apoptosis, and the differential activation of three isoforms of nitric oxide synthases (NOSs), and can exert profound effects on the CVS. Neuronal NOS is one of the three isoforms of NOSs, the others being endothelial (eNOS) and inducible (iNOS) enzymes. Neuronal NOS is a critical homeostatic component of the CVS and plays an important role in regulation of different systems and disease process including nociception. The functional and physiological roles of NO and nNOS are described at the beginning of this review. We also elaborate the structure, gene, domain, and regulation of the nNOS protein. Both inhibitory and excitatory role of nNOS on the sympathetic autonomic nervous system (SANS) and parasympathetic autonomic nervous system (PANS) as mediated via different neurotransmitters/signal transduction processes will be explored, particularly its effects on the CVS. Because the VLM plays a crucial function in cardiovascular homeostatic mechanisms, the neuroanatomy and cardiovascular regulation of the VLM will be discussed in conjunction with the actions of nNOS. Thereafter, we shall discuss the up-to-date developments that are related to the interaction between nNOS and cardiovascular diseases such as hypertension and stroke. Finally, we shall focus on the role of nNOS, particularly within the PAG in cardiovascular regulation and neurotransmission during different types of pain stimulus. Overall, this review focuses on our current understanding of the nNOS protein, and provides further insights on how nNOS modulates, regulates, and controls cardiovascular function during both physiological activity such as exercise, and pathophysiological conditions such as stroke and hypertension. • NOSs catalyze the following reaction: 2 L-arginine + 3 NADPH + 1 H+ + 4 O 2 → 2 citrulline + 2 NO + 4 H 2 O + 3 NADP+. • The glutamate receptor regulating NO production is altered in hypertension and cerebrovascular accidents. • The glutamate receptor regulating NO production is altered in hypertension and cerebrovascular accidents. • The alteration in the nNOS activity within the RVLM and CVLM provides differential roles in neurotransmission release. • The unilateral ischemic stroke differentially affects ipsilateral nNOS protein abundance within the RVLM and the CVLM. [ABSTRACT FROM AUTHOR]

Mayer waves may synchronize overlapping propriobulbar interneuronal microcircuits constituting the respiratory rhythm and pattern generator, sympathetic oscillators, and cardiac vagal preganglionic neurons. Initially described by Sir Sigmund Mayer in the year 1876 in the arterial pressure waveform of anesthetized rabbits, authors have since extensively observed these oscillations in recordings of hemodynamic variables, including arterial pressure waveform, peripheral resistance, and blood flow. Authors would later reveal the presence of these oscillations in sympathetic neural efferent discharge and brainstem and spinal zones corresponding with sympathetic oscillators. Mayer wave central tendency proves highly consistent within, though the specific frequency band varies extensively across, species. Striking resemblance of the Mayer wave central tendency to the species-specific baroreflex resonant frequency has led the majority of investigators to comfortably presume, and generate computational models premised upon, a baroreflex origin of these oscillations. Empirical interrogation of this conjecture has generated variable results and derivative interpretations. Sinoaortic denervation and effector sympathectomy variably reduces or abolishes spectral power contained within the Mayer wave frequency band. Refractorines of Mayer wave generation to barodeafferentation lends credence to the hypothesis these waves are chiefly generated by brainstem propriobulbar and spinal cord propriospinal interneuronal microcircuit oscillators and likely modulated by the baroreflex. The presence of these waves in unitary discharge of medullary lateral tegmental field and rostral ventrolateral medullary neurons (contemporaneously exhibiting fast sympathetic rhythms [2–6 and 10 Hz bands]) in spectral variability in vagotomized pentobarbital-anesthetized and unanesthetized midcollicular (i.e., intercollicular) decerebrate cats supports genesis of Mayer waves by supraspinal sympathetic microcircuit oscillators. Persistence of these waves following high cervical transection in vagotomized unanesthetized midcollicular decerebrate cats would seem to suggest spinal sympathetic microcircuit oscillators generate these waves. The widespread presence of Mayer waves in brainstem sympathetic-related and non-sympathetic-related cells would seem to betray a general tendency of neurons to oscillate at this frequency. We have thus presented an extensive and, hopefully cohesive, discourse evaluating, and evolving the interpretive consideration of, evidence seeking to illumine our understanding of origins of, and insight into mechanisms contributing to, the genesis of Mayer waves. We have predicated our arguments and conjectures in the substance and matter of empirical data, though we have occasionally waxed philosophical beyond these traditional confines in suggesting interpretations exceeding these limits. We believe our synthesis and interpretation of the relevant literature will fruitfully inspire future studies from the perspective of a more intimate appreciation and conceptualization of network mechanisms generating oscillatory variability in neuronal and neural outputs. Our evaluation of Mayer waves informs a novel set of disciplines we term quantum neurophysics extendable to describing subatomic reality. Beyond informing our appreciation of mechanisms generating sympathetic oscillations, Mayer waves may constitute an intrinsic property of neurons extant throughout the cerebrum, brainstem, and spinal cord or reflect an emergent property of interactions between arteriogenic and neuronal oscillations. [ABSTRACT FROM AUTHOR]

Nighttime blood pressure (BP) generally dips by 10% to 20% of the daytime values, and abnormal BP dipping may affect vascular health independently of BP level. The regulation of BP dipping involves arterial baroreflex, whose receptors mainly reside in carotid sinuses and aortic arch. Atherosclerosis in these baroreceptor-resident arteries (BRAs) is frequent among patients with ischemic stroke (IS) and might impair their BP-regulating capacity. We aimed to examine associations between atherosclerosis of BRA and BP dipping in patients with IS. BP dipping ratio was measured by 24-hour ambulatory blood pressure monitoring on the sixth day after IS. With computed tomography angiography, atherosclerosis conditions in 10 segments of carotid sinuses and aortic arch were scored and summed as total atherosclerosis burden of BRA. Among the 245 patients with IS, 78.0% had atherosclerosis in BRA. The total AS burden of BRA was negatively correlated with systolic BP dipping ratio (r=-0.331; P<0.001) and diastolic BP dipping ratio (r=-0.225; P<0.001). After adjusting for age, sex, vascular risk factors, 24-hour BP means, cervical and intracranial atherosclerosis scores, the negative correlations still existed (adjusted β, -0.259 [95% CI, -0.416 to -0.102] and adjusted β, -0.178 [95% CI, -0.346 to -0.010], respectively). In conclusion, higher total atherosclerosis burden of BRA was independently indicative of more blunted dipping of systolic BP and diastolic BP in IS. The total atherosclerosis burden of BRA might be important for predicting and managing BP dipping in patients with IS. [ABSTRACT FROM AUTHOR]

Purpose of Review: Patients with true resistant hypertension (RH) are characterized by having high sympathetic activity and therefore potentially benefit from treatments such as baroreflex amplification (baroreflex activation therapy (BAT) or endovascular baroreflex amplification therapy (EVBA)) or carotid body (CB) modulation. This review aims at providing an up-to-date overview of the available evidence regarding these two therapies. Recent Findings: In recent years, increasing evidence has confirmed the potential of baroreflex amplification, either electrically (Barostim neo) or mechanically (MobiusHD), to improve blood pressure control on short- and long-term with only few side effects, in patients with RH. Two studies regarding unilateral CB resection did not show a significant change in blood pressure. Only limited studies regarding CB modulation showed promising results for transvenous CB ablation, but not for unilateral CB resection. Summary: Despite promising results from mostly uncontrolled studies, more evidence regarding the safety and efficacy from ongoing large randomized sham-controlled trials is needed before baroreflex amplification and CB modulation can be implemented in routine clinical practice. [ABSTRACT FROM AUTHOR]

The sensitization and hypertonicity of visceral afferents are highly relevant to the development and progression of cardiovascular and respiratory disease states. In this review, we described the evidence that the inflammatory process regulates visceral afferent sensitivity and tonicity, affecting the control of the cardiovascular and respiratory system. Some inflammatory mediators like nitric oxide, angiotensin II, endothelin-1, and arginine vasopressin may inhibit baroreceptor afferents and contribute to the baroreflex impairment observed in cardiovascular diseases. Cytokines may act directly on peripheral afferent terminals that transmit information to the central nervous system (CNS). TLR-4 receptors, which recognize lipopolysaccharide, were identified in the nodose and petrosal ganglion and have been implicated in disrupting the blood-brain barrier, which can potentiate the inflammatory process. For example, cytokines may cross the blood-brain barrier to access the CNS. Additionally, pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α and some of their receptors have been identified in the nodose ganglion and carotid body. These pro-inflammatory cytokines also sensitize the dorsal root ganglion or are released in the nucleus of the solitary tract. In cardiovascular disease, pro-inflammatory mediators increase in the brain, heart, vessels, and plasma and may act locally or systemically to activate/sensitize afferent nervous terminals. Recent evidence demonstrated that the carotid body chemoreceptor cells might sense systemic pro-inflammatory molecules, supporting the novel proposal that the carotid body is part of the afferent pathway in the central anti-inflammatory reflexes. The exact mechanisms of how pro-inflammatory mediators affects visceral afferent signals and contribute to the pathophysiology of cardiovascular diseases awaits future research. [ABSTRACT FROM AUTHOR]

Introduction: Resistant hypertension is characterized by an hyperadrenergic tone and by a neurohumoral activation. In this condition drug therapies are unable to obtain a good control of blood pressure and therefore need a contribution from non-pharmachological approach. To this aim it has been hypothesized that to lower blood pressure this could be obtained through stimulation of carotid baroreceptors and modulation of the adrenergic tone. Areas covered: several studies and trials have evaluated the safety and efficacy of two devices-based therapies and this review will discuss the research obtained mainly in resistant hypertensive subjects. Expert opinion: the studies performed have clearly shown the safety and efficacy of these approaches. The stimulation of carotid baroreceptors induces a significant reduction in blood pressure values associated with a reduction in adrenergic tone. The two systems have same limitations. While baroreflex activation therapy has been upgraded to a more simple system, an upgrade of endovascular baroreflex amplification will be able to reduce the side effects. Due to the fact that neurohumoral activation and hyperadrenergic tone are present in several pathophysiological conditions it is possible to assume a wider use of these systems in the future. [ABSTRACT FROM AUTHOR]

The glossopharyngeal nerve, via the carotid sinus nerve (CSN), presents baroreceptors from the internal carotid artery (ICA) and chemoreceptors from the carotid body. Although neurons in the nodose ganglion were labelled after injecting tracer into the carotid body, the vagal pathway to these baro‐ and chemoreceptors has not been identified. Neither has the glossopharyngeal intracranial afferent/sensory pathway that connects to the brainstem been defined. We investigated both of these issues in male Sprague–Dawley rats (n = 40) by injecting neural tracer wheat germ agglutinin‐horseradish peroxidase into: (i) the peripheral glossopharyngeal or vagal nerve trunk with or without the intracranial glossopharyngeal rootlet being rhizotomized; or (ii) the nucleus of the solitary tract right after dorsal and ventral intracranial glossopharyngeal rootlets were dissected. By examining whole‐mount tissues and brainstem sections, we verified that only the most rostral rootlet connects to the glossopharyngeal nerve and usually four caudal rootlets connect to the vagus nerve. Furthermore, vagal branches may: (i) join the CSN originating from the pharyngeal nerve base, caudal nodose ganglion, and rostral or caudal superior laryngeal nerve; or (ii) connect directly to nerve endings in the middle segment of the ICA or to chemoreceptors in the carotid body. The aortic depressor nerve always presents and bifurcates from either the rostral or the caudal part of the superior laryngeal nerve. The vagus nerve seemingly provides redundant carotid baro‐ and chemoreceptors to work with the glossopharyngeal nerve. These innervations confer more extensive roles on the vagus nerve in regulating body energy that is supplied by the cardiovascular, pulmonary and digestive systems. [ABSTRACT FROM AUTHOR]

Baroreceptors play a pivotal role in the regulation of blood pressure through moment to moment sensing of arterial blood pressure and providing information to the central nervous system to make autonomic adjustments to maintain appropriate tissue perfusion. A recent publication by Zeng and colleagues (Zeng WZ, Marshall KL, Min S, Daou I, Chapleau MW, Abboud FM, Liberles SD, Science 362: 464 – 467, 2018) suggests the mechanosensitive ion channels Piezo1 and Piezo2 represent the cellular mechanism by which baroreceptor nerve endings sense changes in arterial blood pressure. However, before Piezo1 and Piezo2 are accepted as the sensor of baroreceptors, the question must be asked of what criteria are necessary to establish this and how well the report of Zeng and colleagues (Zeng WZ, Marshall KL, Min S, Daou I, Chapleau MW, Abboud FM, Liberles SD, Science 362: 464 – 467, 2018) satisfies these criteria. We briefly review baroreceptor function, outline criteria that a putative neuronal sensor of blood pressure must satisfy, and discuss whether the recent findings of Zeng and colleagues suitably meet these criteria. Despite the provocative hypothesis, there are significant concerns regarding the evidence supporting a role of Piezo1/Piezo2 in arterial baroreceptor function. [ABSTRACT FROM AUTHOR]

Systemic anaphylaxis is a life-threatening and allergic reaction that affects various organs. We previously reported that, in the stomach, gastric vasoconstriction occurring at the late phase (15–55 min after injection of ovalbumin antigen) was observed in anesthetized rats sensitized with ovalbumin. In addition, anaphylaxis enhances gastric motility and delays emptying. However, the role of extrinsic autonomic nervous system on antigen-induced gastric alterations was not known. Thus, using the same rat anaphylaxis model, we aimed to determine the changes in the efferent and afferent autonomic nerve activities in the stomach during anaphylactic hypotension. The findings showed that injection of ovalbumin antigen caused substantial systemic hypotension in all sensitized rats. The efferent gastric sympathetic nerve activity (efGSNA), but not the efferent vagal nerve activity, increased only at the early phase (1–10 min after injection of ovalbumin antigen) and showed baroreceptor reflex, as evidenced by a stimulatory response to sodium nitroprusside-induced hypotension. In general, excitation of ef-GSNA could induce pylorus sphincter contraction and gastric vasoconstriction. In the present study, we found that sympathectomy attenuated the anaphylaxis-induced decrease in gastric flux but not the increase in gastric vascular resistance. Thus, the increase in ef-GSNA may cause anaphylactic pylorus sphincter contraction but not anaphylactic gastric vasoconstriction. On the other hand, the afferent gastric vagal nerve activity, but not the afferent sympathetic nerve activity, increased during the early phase of anaphylactic hypotension. However, vagotomy produced no effects on the anaphylactic gastric dysfunction. In conclusion, the gastric sympathetic nerves partly modulate stomach function during systemic anaphylaxis. [ABSTRACT FROM AUTHOR]

Smoking is a risk factor for cardiovascular diseases. Prior reports showed a transient increase in blood pressure (BP) following a spontaneous burst of muscle sympathetic nerve activity (MSNA). We hypothesized that this pressor response would be accentuated in smokers. Using signal-averaging techniques, we examined the BP (Finometer) response to MSNA in 18 otherwise healthy smokers and 42 healthy nonsmokers during resting conditions. The sensitivities of baroreflex control of MSNA and heart rate were also assessed. The mean resting MSNA, heart rate, and mean arterial pressure (MAP) were higher in smokers than nonsmokers. The MAP increase following a burst of MSNA was significantly greater in smokers than nonsmokers (Δ3.4 ± 0.3 vs. Δ1.6 ± 0.1 mmHg, P < 0.001). The baroreflex sensitivity (BRS) of burst incidence, burst area, or total activity was not different between the two groups. However, cardiac BRS was lower in smokers than nonsmokers (14.6 ± 1.7 vs. 24.6 ± 1.5 ms/mmHg, P < 0.001). Moreover, the MAP increase following a burst was negatively correlated with the cardiac BRS. These observations suggest that habitual smoking in otherwise healthy individuals raises the MAP increase following spontaneous MSNA and that the attenuated cardiac BRS in the smokers was a contributing factor. We speculate that the accentuated pressor increase in response to spontaneous MSNA may contribute to the elevated resting BP in the smokers. [ABSTRACT FROM AUTHOR]

Maintaining an equilibrium between oxygen supply and demand is a principal function of the cardiovascular system. In times of altered metabolic demand mechanisms exist to maintain the balance between supply and demand. Exercise, haemorrhage and pregnancy all lead to changes in oxygen demand and subsequently modification of cardiac output. During isotonic exercise, metabolic demands of muscle are greatly increased. Sympathetic stimulation and inhibition of the parasympathetic system lead to increases in heart rate and venous return, increasing cardiac output. This allows a proportional increase in blood flow to the exercising muscle. Cardiac output increases throughout pregnancy. In the first and second trimesters this rise is mainly due to an increase in stroke volume, however during the later stages of pregnancy stroke volume reaches a plateau and further increase in cardiac output is mediated by a rising heart rate. In contrast, during haemorrhage, decreased venous return leads to a reduction in cardiac output, with a baroreceptor response due to the drop in arterial blood pressure. The tachycardia and vasoconstriction which follows are compensatory mechanisms in an attempt to preserve blood pressure. The Valsalva manoeuvre illustrates several aspects of reflex control of the cardiovascular system and allows non-invasive assessment and quantification of control mechanisms. Changes in stroke volume during the respiratory cycle can be used to predict fluid responsiveness and can be measured as pulse pressure variation or stroke volume variation. [ABSTRACT FROM AUTHOR]

Clinical trials and animal experimental studies have demonstrated an association of arterial baroreflex impairment with the prognosis and mortality of cardiovascular diseases and diabetes. As a primary part of the arterial baroreflex arc, the pressure sensitivity of arterial baroreceptors is blunted and involved in arterial baroreflex dysfunction in cardiovascular diseases and diabetes. Changes in the arterial vascular walls, mechanosensitive ion channels, and voltage-gated ion channels contribute to the attenuation of arterial baroreceptor sensitivity. Some endogenous substances (such as angiotensin II and superoxide anion) can modulate these morphological and functional alterations through intracellular signaling pathways in impaired arterial baroreceptors. Arterial baroreceptors can be considered as a potential therapeutic target to improve the prognosis of patients with cardiovascular diseases and diabetes. [ABSTRACT FROM AUTHOR]