Renin Cell Baroreceptor, a Nuclear Mechanotransducer Central for Homeostasis.

[Figure: see text].

Effects of carotid baroreceptor stimulation on aortic remodeling in obese rats.

BACKGROUND AND AIM: Our previous study found carotid baroreceptor stimulation (CBS) reduces body weight and white adipose tissue (WAT) weight, restores abnormal secretion of adipocytokines and inflammation factors, decreases systolic blood pressure (SBP) by inhibiting activation of sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in obese rats. In this study, we explore effects of CBS on aortic remodeling in obese rats. METHODS AND RESULTS: Rats were fed high-fat diet (HFD) for 16 weeks to induce obesity and underwent either CBS device implantation and stimulation or sham operation at 8 weeks. BP and body weight were measured weekly. RAS activity of WAT, histological, biochemical and functional profiles of aortas were detected after 16 weeks. CBS effectively decreased BP in obese rats, downregulated mRNA expression of angiotensinogen (AGT) and renin in WAT, concentrations of AGT, renin, angiotensin II (Ang II), protein levels of Ang II receptor 1 (AT1R) and Ang II receptor 2 (AT2R) in WAT were declined. CBS inhibited reactive oxygen species (ROS) generation, inflammatory response and endoplasmic reticulum (ER) stress in aortas of obese rats, restrained vascular wall thickening and vascular smooth muscle cells (VSMCs) phenotypic switching, increased nitric oxide (NO) synthesis, promoted endothelium-dependent vasodilatation by decreasing protein expression of AT1R and leptin receptor (LepR), increasing protein expression of adiponectin receptor 1 (AdipoR1) in aortic VSMCs. CONCLUSION: CBS reduced BP and reversed aortic remodeling in obese rats, the underlying mechanism might be related to the suppressed SNS activity, restored adipocytokine secretion and restrained RAS activity of WAT.

Cost-impact analysis of baroreflex activation therapy in chronic heart failure patients in the United States.

BACKGROUND: The study evaluated the cost of baroreflex activation therapy plus guideline directed therapy (BAT + GDT) compared to GDT alone for HF patients with reduced ejection fraction and New York Heart Association Class III or II (with a recent history of III). Baroreflex activation therapy (BAT) is delivered by an implantable device that stimulates the baroreceptors through an electrode attached to the outside of the carotid artery, which rebalances the autonomic nervous system to regain cardiovascular (CV) homeostasis. The BeAT-HF trial evaluated the safety and effectiveness of BAT. METHODS: A cost impact model was developed from a U.S. health care payer or integrated delivery network perspective over a 3-year period for BAT + GDT versus GDT alone. Expected costs were calculated by utilizing 6-month data from the BeAT-HF trial and existing literature. HF hospitalization rates were extrapolated based on improvement in NT-proBNP. RESULTS: At baseline the expected cost of BAT + GDT were $29,526 per patient more than GDT alone due to BAT device and implantation costs. After 3 years, the predicted cost per patient was $9521 less expensive for BAT + GDT versus GDT alone due to lower rates of significant HF hospitalizations, CV non-HF hospitalizations, and resource intensive late-stage procedures (LVADs and heart transplants) among the BAT + GDT group. CONCLUSIONS: BAT + GDT treatment becomes less costly than GDT alone beginning between years 1 and 2 and becomes less costly cumulatively between years 2 and 3, potentially providing significant savings over time. As additional BeAT-HF trial data become available, the model can be updated to show longer term effects.

Impairments in Blood Pressure Regulation and Cardiac Baroreceptor Sensitivity Among Patients With Heart Failure Supported With Continuous-Flow Left Ventricular Assist Devices.

BACKGROUND: Continuous-flow (CF) left ventricular assist devices (LVADs) improve outcomes for patients with advanced heart failure (HF). However, the lack of a physiological pulse predisposes to side-effects including uncontrolled blood pressure (BP), and there are little data regarding the impact of CF-LVADs on BP regulation. METHODS: Twelve patients (10 males, 60±11 years) with advanced heart failure completed hemodynamic assessment 2.7±4.1 months before, and 4.3±1.3 months following CF-LVAD implantation. Heart rate and systolic BP via arterial catheterization were monitored during Valsalva maneuver, spontaneous breathing, and a 0.05 Hz repetitive squat-stand maneuver to characterize cardiac baroreceptor sensitivity. Plasma norepinephrine levels were assessed during head-up tilt at supine, 30o and 60o. Heart rate and BP were monitored during cardiopulmonary exercise testing. RESULTS: Cardiac baroreceptor sensitivity, determined by Valsalva as well as Fourier transformation and transfer function gain of Heart rate and systolic BP during spontaneous breathing and squat-stand maneuver, was impaired before and following LVAD implantation. Norepinephrine levels were markedly elevated pre-LVAD and improved-but remained elevated post-LVAD (supine norepinephrine pre-LVAD versus post-LVAD: 654±437 versus 323±164 pg/mL). BP increased during cardiopulmonary exercise testing post-LVAD, but the magnitude of change was modest and comparable to the changes observed during the pre-LVAD cardiopulmonary exercise testing. CONCLUSIONS: Among patients with advanced heart failure with reduced ejection fraction, CF-LVAD implantation is associated with modest improvements in autonomic tone, but persistent reductions in cardiac baroreceptor sensitivity. Exercise-induced increases in BP are blunted. These findings shed new light on mechanisms for adverse events such as stroke, and persistent reductions in functional capacity, among patients supported by CF-LVADs. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03078972.

The protective role of SOD1 overexpression in central mediation of bradycardia following chronic intermittent hypoxia in mice.

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder that is associated with many cardiovascular complications. Similar to OSA, chronic intermittent hypoxia (CIH) (a model for OSA) leads to oxidative stress and impairs baroreflex control of the heart rate (HR) in rodents. The baroreflex arc includes the aortic depressor nerve (ADN), vagal efferent, and central neurons. In this study, we used mice as a model to examine the effects of CIH on baroreflex sensitivity, aortic baroreceptor afferents, and central and vagal efferent components of the baroreflex circuitry. Furthermore, we tested whether human Cu/Zn Superoxide Dismutase (SOD1) overexpression in transgenic mice offers protection against CIH-induced deficit of the baroreflex arc. Wild-type C57BL/6J and SOD1 mice were exposed to room air (RA) or CIH and were then anesthetized, ventilated, and catheterized for measurement of mean arterial pressure (MAP) and HR. Compared with wild-type RA control, CIH impaired baroreflex sensitivity but increased maximum baroreceptor gain and bradycardic response to vagal efferent stimulation. Additionally, CIH reduced the bradycardic response to ADN stimulation, indicating a diminished central regulation of bradycardia. Interestingly, SOD1 overexpression prevented CIH-induced attenuation of HR responses to ADN stimulation and preserved HR responses to vagal efferent stimulation in transgenic mice. We suggest that CIH decreased central mediation of the baroreflex and SOD1 overexpression may prevent the CIH-induced central deficit.

Early Signs of Sinoatrial Reinnervation in the Transplanted Heart.

BACKGROUND: Heart transplantation (HTx) surgically transects all connections to the heart, including the autonomic nerves. We prospectively examined signs, timing and consequences of early sympathetic and parasympathetic sinoatrial reinnervation, as well as explored indirect evidence of afferent cardiopulmonary reinnervation. METHODS: Fifty HTx recipients were assessed at 2.5, 6, and 12 mo after HTx. For comparison, 50 healthy controls were examined once. Continuous, noninvasive recordings of hemodynamic variables and heart rate variability indices were performed at supine rest, 0.2 Hz controlled breathing, 60° head-up-tilt, during the Valsalva maneuver and during handgrip isometric exercise. RESULTS: In HTx recipients, supine low-frequency heart rate variability gradually increased; supine high-frequency variability did not change; heart rate variability indices during controlled breathing remained unaltered; heart rate responses during tilt and isometric exercise gradually increased; the tachycardia response during Valsalva maneuver increased, while the bradycardia response remained unchanged; and indices of baroreflex sensitivity improved. Responses remained low compared to healthy controls. A negative correlation between indices of preload and heart rate response during head-up tilt emerged at 12 mo. CONCLUSIONS: Results suggest that sympathetic reinnervation of the sinoatrial node starts within 6 mo after HTx and strengthens during the first year. No evidence of early parasympathetic reinnervation was found. Indirect signs of afferent reinnervation of cardiopulmonary low-pressure baroreceptors emerged at 12 mo. Better sympathetic sinoatrial control improved heart rate responsiveness to orthostatic challenge and isometric exercise, as well as heart rate buffering of blood pressure fluctuations.

A Paradoxical Vasodilatory Nutraceutical Intervention for Prevention and Attenuation of Migraine-A Hypothetical Review.

Studies suggest that migraine pain has a vascular component. The prevailing dogma is that peripheral vasoconstriction activates baroreceptors in central, large arteries. Dilatation of central vessels stimulates nociceptors and induces cortical spreading depression. Studies investigating nitric oxide (NO) donors support the indicated hypothesis that pain is amplified when acutely administered. In this review, we provide an alternate hypothesis which, if substantiated, may provide therapeutic opportunities for attenuating migraine frequency and severity. We suggest that in migraines, heightened sympathetic tone results in progressive central microvascular constriction. Suboptimal parenchymal blood flow, we suggest, activates nociceptors and triggers headache pain onset. Administration of NO donors could paradoxically promote constriction of the microvasculature as a consequence of larger upstream central artery vasodilatation. Inhibitors of NO production are reported to alleviate migraine pain. We describe how constriction of larger upstream arteries, induced by NO synthesis inhibitors, may result in a compensatory dilatory response of the microvasculature. The restoration of central capillary blood flow may be the primary mechanism for pain relief. Attenuating the propensity for central capillary constriction and promoting a more dilatory phenotype may reduce frequency and severity of migraines. Here, we propose consideration of two dietary nutraceuticals for reducing migraine risk: L-arginine and aged garlic extracts.

Tentonin 3/TMEM150C senses blood pressure changes in the aortic arch.

The baroreceptor reflex is a powerful neural feedback that regulates arterial pressure (AP). Mechanosensitive channels transduce pulsatile AP to electrical signals in baroreceptors. Here we show that tentonin 3 (TTN3/TMEM150C), a cation channel activated by mechanical strokes, is essential for detecting AP changes in the aortic arch. TTN3 was expressed in nerve terminals in the aortic arch and nodose ganglion (NG) neurons. Genetic ablation of Ttn3 induced ambient hypertension, tachycardia, AP fluctuations, and impaired baroreflex sensitivity. Chemogenetic silencing or activation of Ttn3+ neurons in the NG resulted in an increase in AP and heart rate, or vice versa. More important, overexpression of Ttn3 in the NG of Ttn3-/- mice reversed the cardiovascular changes observed in Ttn3-/- mice. We conclude that TTN3 is a molecular component contributing to the sensing of dynamic AP changes in baroreceptors.

Total Atherosclerosis Burden of Baroreceptor-Resident Arteries Independently Predicts Blood Pressure Dipping in Patients With Ischemic Stroke.

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 ß, -0.259 [95% CI, -0.416 to -0.102] and adjusted ß, -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.

Impact of antihypertensive treatment on resiliency to clinical pain.

OBJECTIVES: Although progress has been made in the regulation of hypertension over the past decades, the USA and some other countries have faced a significant rise in incidence of chronic pain management cases during the same period. Studies of the relationship between pain and blood pressure (BP) regulations propose that these two processes may be interconnected. Studies of effects of antihypertensive treatment on pain in general and its chronification have never been reviewed. METHODS: A narrative review of respective studies with analysis of credibility of the findings was conducted. RESULTS: Some studies have suggested that aggressive reduction of high BP may contribute to a return in pain symptoms and may require more aggressive, long-term pain management. Other studies propose that long-term antihypertensive medication could also increase the risk for new cases of chronic pain. Pain initiates a central neuroplastic resetting of the baroreceptor activation accounting for sustained increase of BP with an adaptive 'pain-killing' or maladaptive 'pain-complication' effect associated with pain chronification, and these mechanisms may be moderated by antihypertensive medications. However, different antihypertensive drugs and nondrug treatments may diversely affect pain mechanisms at different stages of treatments. CONCLUSION: Uncontrollable reduction of high BP in some patients with hypertension could increase the risk for chronic pain incidence and its severity. Practical recommendations in BP control should be reconsidered to take into account patients' chronic pain. Further research is needed of moderation effects of different antihypertensive manipulations on pain to improve pain management in these patients.

New approaches for treating atrial fibrillation: Focus on autonomic modulation.

Atrial fibrillation (AF) is a rapidly growing clinical problem in routine practice, both for cardiologists as well as general practitioners. Current therapies aimed at the management of AF include anti-arrhythmic drug therapy and catheter ablation. These therapies have a number of limitations and risks, and have disappointing long-term efficacy in maintaining sinus rhythm and improving hard clinical outcomes. Because of this, there is growing interest in pursuing alternative management strategies in patients with AF. This review seeks to highlight emerging AF therapies, with a specific focus on several modalities aimed at modulation of the autonomic nervous system. These therapies have shown promise in early pre-clinical and clinical trials, and represent exciting alternatives to standard AF treatment.

Transient Receptor Potential Vanilloid 4 Regulation of Adenosine Triphosphate Release by the Adenosine Triphosphate Transporter Vesicular Nucleotide Transporter, a Novel Therapeutic Target for Gastrointestinal Baroreception and Chronic Inflammation.

BACKGROUND: Transient receptor potential vanilloid 4 (TRPV4) is activated by stretch (mechanical), warm temperature, some epoxyeicosatrienoic acids, and lipopolysaccharide. TRPV4 is expressed throughout the gastrointestinal epithelia and its activation induces adenosine triphosphate (ATP) exocytosis that is involved in visceral hypersensitivity. As an ATP transporter, vesicular nucleotide transporter (VNUT) mediates ATP storage in secretory vesicles and ATP release via exocytosis upon stimulation. SUMMARY: TRPV4 is sensitized under inflammatory conditions by a variety of factors, including proteases and serotonin, whereas methylation-dependent silencing of TRPV4 expression is associated with various pathophysiological conditions. Gastrointestinal epithelia also release ATP in response to hypo-osmolality or acid through molecular mechanisms that remain unclear. These synergistically released ATP could be involved in visceral hypersensitivity. Low concentrations of the first generation bisphosphate, clodronate, were recently reported to inhibit VNUT activity and thus clodronate may be a safe and potent therapeutic option to treat visceral pain. Key Messages: This review focuses on: (1) ATP and TRPV4 activities in gastrointestinal epithelia; (2) factors that could modulate TRPV4 activity in gastrointestinal epithelia; and (3) the inhibition of VNUT as a potential novel therapeutic strategy for functional gastrointestinal disorders.

Multiannual, Intensive Strength-Endurance Training Modulates the Activity of the Cardiovascular and Autonomic Nervous System among Rowers of the International Level.

INTRODUCTION: Professional athlete training is significantly different from recreational physical activity, and sustained, repetitive exposure to over-strenuous and intensive training may result in critical changes of most systems and organs in a sportsman's body. AIM: The assessment of the influence of multiannual strength-endurance training on the autonomic nervous system (ANS) and cardiovascular system (CVS) among the rowers of Polish national team. MATERIALS AND METHODS: 20 rowers, aged 20-30, seniors of Polish national team were qualified into the study. The functional examination of ANS was conducted by means of Task Force® Monitor system. The assessed parameters included hemodynamic parameters, heart rate, and blood pressure variability and reflexes sensitivity of baroreceptors. In order to examine and compare the reaction of autonomic nervous system the subjects underwent a tilt test. RESULTS: In the study group, significantly higher levels of sBP (129.3 ± 12.2 vs 118.3 ± 8.4, p = 0.0030), SI (59.9 ± 8.8 vs 41.2 ± 6.8, p > 0.001), CI (3.2 ± 0.5 vs 2.4 ± 0.4, p > 0.001), and significantly lower levels of HR (54.2 ± 5.3 vs 60.1 ± 5.7, p = 0.0034) and TPRI (2333.3 ± 389.9 vs 2950.2 ± 604.2, p = 0.0012) compared to the control group, were found. After the tilt test the levels of HR (p = 0.0005) and TPRI (p = 0.0128) were significantly higher but SI (p > 0.001) and CI (p = 0.0006) were significantly lower in the study group compared to the control. CONCLUSIONS: Multiannual strength-endurance training connected with rowing activities substantially modulates the activity of cardiovascular and autonomic nervous system, influences the volumetric workload of the heart and structural changes, and increases the sensitivity of reflexes of arterial baroreceptors.

Exercise Pressor Reflex Contributes to the Cardiovascular Abnormalities Characterizing: Hypertensive Humans During Exercise.

We investigated the impact of hypertension on circulatory responses to exercise and the role of the exercise pressor reflex in determining the cardiovascular abnormalities characterizing patients with hypertension. After a 7-day drug washout, 8 hypertensive (mean arterial pressure [MAP] 130±4 mm Hg; 65±3 years) and 8 normotensive (MAP 117±2 mm Hg; 65±2 years) individuals performed single-leg knee-extensor exercise (7 W, 15 W, 50%, 80%-Wpeak) under control conditions and with lumbar intrathecal fentanyl impairing feedback from µ-opioid receptor-sensitive leg muscle afferents. Femoral artery blood flow (QL), MAP (femoral artery), leg vascular conductance, and changes in cardiac output were continuously measured. While the increase in MAP from rest to control exercise was significantly greater in hypertension compared with normotension, the exercise-induced increase in cardiac output was comparable between groups, and QL and leg vascular conductance responses were ≈18% and ≈32% lower in the hypertensive patients (P<0.05). The blockade-induced decreases in MAP were significantly larger during exercise in hypertensive (≈11 mm Hg) compared with normotensive (≈6 mm Hg). Afferent blockade attenuated the central hemodynamic response to exercise similarly in both groups resulting in a ≈15% lower cardiac output at each workload. With no effect in normotensive, afferent blockade significantly raised the peripheral hemodynamic response to exercise in hypertensive, resulting in ≈14% and ≈23% higher QL and leg vascular conductance during exercise. Finally, QL and MAP during fentanyl-exercise in hypertensive were comparable to that of normotensive under control conditions (P>0.2). These findings suggest that exercise pressor reflex abnormalities largely account for the exaggerated MAP response and the impaired peripheral hemodynamics during exercise in hypertension.

Pulmonary Artery Denervation: Update on Clinical Studies.

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.

Cardiovascular phenotyping for personalized lifestyle treatments of chronic abdominal pain in Irritable Bowel Syndrome: A randomized pilot study.

BACKGROUND: Different physical exercise interventions for pain and other related symptoms largely follow non-personalized guidelines and show a high degree of variability in outcome. These interventions are considered to have different pathways toward improvement in autonomic regulation of energy metabolism. The current pilot study was conducted to assess the predictive value of individual cardiovascular (CV) activity markers at rest to predict clinical outcomes for two popular exercise-based interventions (walking and yoga) in patients with Irritable Bowel Syndrome (IBS). METHODS: Twenty-seven adult participants with IBS were randomly assigned to a 16-biweekly Iyengar yoga or walking program. They completed pre- and post-treatment assessments on IBS symptom severity, affective and somatic complaints, and various measures of resting autonomic function including blood pressure (BP), heart rate and its variability, baroreceptor sensitivity (BRS) to activations and inhibitions with gains of brady- and tachycardiac baro-responses, and BP start points for these spontaneous baroreflexes. RESULTS: Pretreatment BRS was differentially related to clinical response for the treatment groups. Specifically, a significant decrease in pain severity was found in response to yoga for those participants who had lower resting BRS to activations, but decreased pain severity was associated with higher resting BRS for those in the walking group. The effect was not related to affective symptom relief. Other CV measures showed similar associations with clinical outcomes for both groups. CONCLUSIONS: The data suggest therefore that CV based phenotypes may be useful in personalizing clinical interventions for IBS. They may also point to autonomic mechanisms that are targets for such interventions.

Hydraulic stimulation of carotid artery baroreceptors as a likely cause of transient asystolic cardiac arrest during diagnostic angiography or surgical endarterectomy.

We describe two patients-both who underwent general anesthesia-in whom we theorize that hydraulic pressure on carotid artery baroreceptors resulted in transient asystolic cardiac arrest (TACA) during diagnostic or therapeutic procedures. Patient #1 was a 58-year-old female who experienced TACA in response to rapid injection of radiocontrast material into the carotid artery during diagnostic cerebral angiography. Her history was remarkable for aneurysmal subarachnoid hemorrhage at least 13 hr prior to angiography, radiographic evidence of intracranial hypertension, and baseline bradycardia, collectively suggestive of increases in baseline vagal tone. Potentially contributing to TACA, the patient had a 90° curve in the internal carotid artery, just distal to the carotid bifurcation and tip of the angiography catheter, that likely diminished runoff of injected contrast solution and, in turn, would have exacerbated any intracarotid pressure increases in response to injection. There was no evidence of increased baseline vagal tone in Patient #2, a 79-year-old female having carotid endarterectomy surgery. She experienced TACA immediately after full release of an occlusive clamp on the common carotid artery proximal to the now closed carotid arteriotomy, but while the internal carotid was still occluded. Of note, the carotid artery baroreceptors were not treated with local anesthetic in these patients, thus they should have retained much of their normal function. We describe the possible pathomechanisms involved in TACA in these patients, measures to diminish the likelihood of the phenomenon occurring in future patients, and methods for treating the asystole.

Carotid Endarterectomy with Autoarterial Remodeling of Bifurcation of the Common Carotid Artery and Carotid Endarterectomy with Patch Closure: Comparison of Methods.

BACKGROUND: The objectives of our research were to identify whether the new method of carotid endarterectomy (CEA) with autoarterial remodeling of bifurcation of the common carotid artery (ARBCCA) influences daily parameters of blood pressure and heart rate (HR) while monitoring them on a daily basis and to assess the efficacy of the suggested method. MATERIALS AND METHODS: It is a prospective randomized comparative study. The first group (n = 100) included patients that underwent ARBCCA, the second group (n = 100) included patients that underwent "classic" CEA with xenopericardial patch closure. Diurnal Holter recording of blood pressure and (HR) was performed before and after the surgical treatment in both groups. RESULTS: Surgical treatment in both groups leads to an increase of HR, arterial hypertension time index by systolic blood pressure, and arterial hypertension time index by diastolic arterial blood pressure. The damage of carotid artery bulb increases sympathetic innervation and causes dysregulation of the baroreceptor mechanism. CONCLUSIONS: In our study, we did not reveal a significant difference in the incidence of postoperative hypertension and the dependence of HR on the choice of surgical technique. Thus, the proposed ARBCCA method does not lead to an increased risk of pre-existing arterial hypertension development. A significant difference is found out on the parameter of the clamping time of carotid arteries in favor to ARBCCA group. Another advantage of the suggested technique is the number of restenosis greater than 50% during the 2-year follow-up (4 [4%] cases (ARBCCA group) versus 12 [12%] cases ["classic" CEA], respectively, P = .037).

Kidney protective effects of baroreflex activation therapy in patients with resistant hypertension.

Baroreflex activation therapy (BAT) is approved for the treatment of resistant hypertension. In addition to blood pressure (BP) reduction, pilot studies suggested several organoprotective effects of BAT. Thirty-two patients with resistant hypertension were prospectively treated with BAT. Besides office BP and 24-hour ambulatory BP (ABP) measurements, detection of a urinary proteome-based classifier (CKD273), which has been shown to predict chronic kidney disease (CKD) progression, was carried out at baseline and after 6 months of BAT. Office BP significantly decreased from 170 ± 25/90 ± 18 to 149 ± 29/82 ± 18 mm Hg. Analysis of CKD273 score and eGFR with CKD-EPI equation at baseline revealed strong correlation (r = 0.568, P < 0.001). After 6 months of BAT, there was no significant change in CKD273 score (-0.061 [95% CI: -0.262 to 0.140], P = 0.601). However, by stratification of the data regarding ABP response, there was a statistically significant (P = 0.0113) reduction in the CKD273 score from a mean of 0.161 [95% CI: -0.093 to 0.414] to -0.346 [95% CI: -0.632 to -0.060] after BAT in patients with systolic ABP decrease of ≥5 mm Hg. These data emphasized potential nephroprotective effects of BAT in patients with sufficient BP response.

Altered arterial baroreflex-muscle metaboreflex interaction in heart failure.

Two powerful reflexes controlling cardiovascular function during exercise are the muscle metaboreflex and arterial baroreflex. In heart failure (HF), the strength and mechanisms of these reflexes are altered. Muscle metaboreflex activation (MMA) in normal subjects increases mean arterial pressure (MAP) primarily via increases in cardiac output (CO), whereas in HF the mechanism shifts to peripheral vasoconstriction. Baroreceptor unloading increases MAP via peripheral vasoconstriction, and this pressor response is blunted in HF. Baroreceptor unloading during MMA in normal animals elicits an enormous pressor response via combined increases in CO and peripheral vasoconstriction. The mode of interaction between these reflexes is intimately dependent on the parameter (e.g., MAP and CO) being investigated. The interaction between the two reflexes when activated simultaneously during dynamic exercise in HF is unknown. We activated the muscle metaboreflex in chronically instrumented dogs during mild exercise (via graded reductions in hindlimb blood flow) followed by baroreceptor unloading [via bilateral carotid occlusion (BCO)] before and after induction of HF. We hypothesized that BCO during MMA in HF would cause a smaller increase in MAP and a larger vasoconstriction of ischemic hindlimb vasculature, which would attenuate the restoration of blood flow to ischemic muscle observed in normal dogs. We observed that BCO during MMA in HF increases MAP by substantial vasoconstriction of all vascular beds, including ischemic active muscle, and that all cardiovascular responses, except ventricular function, exhibit occlusive interaction. We conclude that vasoconstriction of ischemic active skeletal muscle in response to baroreceptor unloading during MMA attenuates restoration of hindlimb blood flow. NEW & NOTEWORTHY We found that baroreceptor unloading during the muscle metaboreflex in heart failure results in occlusive interaction (except for ventricular function) with significant vasoconstriction of all vascular beds. In addition, restoration of blood flow to ischemic active muscle, via preferentially larger vasoconstriction of nonischemic beds, is significantly attenuated in heart failure.