Sympathetic nervous system activation is a hallmark of high-altitude hypoxia, yet the afferent mechanisms remain incompletely defined. We examined the relative contributions of pulmonary arterial mechanoreceptors and carotid chemoreceptors - two excitatory pathways co-activated by hypoxia - to sustained sympathoexcitation at altitude. Nine healthy lowlanders (27±7years, three female) were studied after 6-9days at 3800m under four conditions: (1) control, (2) inhaled nitric oxide (iNO, 40ppm) to reduce pulmonary arterial pressure, (3) low-dose dopamine infusion (2µgkg- 1min- 1) to suppress the carotid chemoreflex, and (4) combined iNO and dopamine. End-tidal oxygen and carbon dioxide were kept constant throughout. We assessed muscle sympathetic nerve activity (MSNA), systemic haemodynamics, ventilation and pulmonary arterial systolic pressure. iNO reduced pulmonary arterial pressure and significantly decreased MSNA (condition 1: 25±8 burstsmin-1 vs. condition 2: 21±7 burstsmin-1; P=0.0415), whereas dopamine infusion reduced ventilation (P<0.001) without a consistent effect on MSNA (condition 1: 25±8 burstsmin-1 vs. condition 3: 28±13 burstsmin-1; P=0.112). Combined intervention produced a small reduction in sympathetic nerve activity (condition 3: 28±13 burstsmin-1 vs. condition 4: 26±13 burstsmin-1; P=0.0643), likely due to baroreflex engagement. These findings confirm that unloading pulmonary arterial pressure attenuates MSNA, reinforcing the role of pulmonary mechanoreceptors in high altitude sympathoexcitation. Attempts to isolate a carotid chemoreflex contribution were likely confounded by dopamine's haemodynamic effect, which introduced variability and limited the specificity of this intervention. Thus, interpretation of this component remains exploratory, highlighting the integrative complexity of reflex control of high altitude sympathoexcitation in humans.

This study aimed to investigate the efficacy and safety of short-term high- and moderate-intensity interval training (HIIT and MIIT) in high-risk patients with cardiovascular disease (CVD). We retrospectively recruited 161 high-risk patients with CVD that completed 4 weeks of exercise training in a cardiac rehabilitation clinic between February 2021 and June 2023; 80 patients underwent HIIT, and 81 underwent MIIT. The MIIT contained 4 sets×8 minutes at a rating of perceived exertion of 12 to 14 on the Borg scale of 6 to 20 with 2 minutes of rest between sets. The HIIT consisted of 20 cycles × 30 seconds at a rating of perceived exertion of 15 to 17 with 30 seconds of rest between cycles. The median age was 54 years, and 65% were male. After 4 weeks, mean peak oxygen uptake (), at the anaerobic threshold, and oxygen pulse in HIIT versus MIIT increased by 2.6 versus 2.8 mL/kg/min, 1.7 versus 1.8 mL/kg/min, and 1.2 versus 0.9 mL/beat, respectively (P <.001). The resting systolic and diastolic blood pressures both decreased after HIIT and MIIT (all P<.05). Few exercise-related mild adverse events (<1%) occurred during HIIT and MIIT, and compliance did not differ between groups (P =.779). Our findings suggested that both HIIT and MIIT demonstrated improvements in , at anaerobic threshold, and oxygen pulse as well as reductions in blood pressure after 4 weeks of exercise training. No serious cardiac events occurred during the exercise training. Both HIIT and MIIT can be considered efficient and safe therapeutic methods for high-risk patients with CVD.

Background General anesthesia frequently causes atelectasis, a condition that significantly endangers patient safety during and after surgery, especially in neonates. Evidence suggests that lung protective ventilation (LPV) strategies may reduce the incidence of postoperative atelectasis in patients receiving general anaesthesia; however, the efficacy for neonatal patients remains controversial. This study aims to explore how LPV affects the incidence of atelectasis in neonates. Methods This randomized controlled trial involved neonatal patients under general anesthesia with mechanical ventilation for over two hours, randomly assigned to receive LPV (including a Vt of 6 mL/kg, 5 cmH 2 O PEEP, and lung RMs once per hour) or conventional ventilation (including a Vt of 8–10 mL/kg without PEEP or RMs). Each infant underwent two lung ultrasound (LUS) scans at specified time points: 5 min post-intubation and at the conclusion of surgery. Additionally, three arterial blood gas analyses were conducted for each infant at T1 (5 min post-intubation), T2 (one hour after mechanical ventilation), and T3 (two hours after mechanical ventilation). HR and MAP were recorded at four time points: T1, T2, T3, and T4 (at the conclusion of surgery). The primary outcomes were the incidence of significant atelectasis (defined as any area with a consolidation score of ≥2) and LUS scores at the conclusion of surgery. Results The study enrolled 100 neonatal patients, divided into 50 in the LPV group and 50 in the control group. At the conclusion of surgery, the LPV group had a significantly lower incidence of significant atelectasis (18% vs. 58%) and lower median LUS scores [7 [6, 9] vs. 12 [8, 18]] than the control group did (all P &amp;lt; 0.001). In addition, there were differences in the partial pressure of arterial oxygen (PaO₂) and partial pressure of arterial carbon dioxide (PaCO₂) between the two groups at T2 and T3, although both were within the normal range. No significant differences were observed in HR, MAP or the rate of respiratory events after surgery between the two groups. Conclusions Compared with conventional ventilation, LPV results in a significantly lower incidence of significant postoperative atelectasis and lower LUS scores in neonates receiving general anaesthesia. Clinical Trial Registration ClinicalTrials.gov , ChiCTR2100051721

Objective: To explore the relationship between anesthetic depth and surgical stress response in minimally invasive cardiothoracic surgery. Methods: A total of 89 patients who underwent thoracoscopic minimally invasive cardiothoracic surgery in our hospital from June 2024 to December 2024 were selected as the research objects. They were divided into the light anesthesia group (n = 45) and the deep anesthesia group (n = 44). The vital signs at different intraoperative nodes and perioperative stress status of the two groups were compared. Results: Before lesion resection and after surgery, the mean arterial pressure and heart rate of the deep anesthesia group were lower than those of the light anesthesia group, with statistically significant differences. Conclusion: In thoracoscopic minimally invasive cardiothoracic surgery, deep anesthesia can effectively control the patient’s surgical stress response, but the postoperative awakening time is longer; patients under light anesthesia have a shorter awakening time, but the intraoperative stress response is obvious.

Cardiac operations with cardiopulmonary bypass (CPB) trigger a systemic inflammatory response. To understand the underlying mechanisms behind the biological reactions during CPB, rat models that mimic clinical CPB have been developed. Previously, a rat CPB model incorporating an intraluminal flow oxygenator was employed to accommodate the limited blood volume of rats. This study aimed to evaluate a rat CPB model incorporating an extraluminal flow oxygenator. The effective membrane area and priming volume of the extraluminal flow oxygenator were 0.0236 m2 and 3.0 mL, respectively. Rats were divided into three groups: (i) SHAM group (surgical preparation only); (ii) CPB with intraluminal flow oxygenator group (CPB Int-oxy); and (iii) CPB with extraluminal flow oxygenator group (CPB Ext-oxy). Blood samples were collected before and at 60 and 120 min after CPB initiation. Hemodynamics, blood gases, blood cell counts (RBC, WBC, PLT), and inflammatory responses (IL-6, IL-10, TNF-α) were measured. Each CPB group maintained an arterial pressure and Hb at approximately 75 mmHg and 9.5%, respectively, without blood transfusion, and an oxygenation and carbon dioxide removal from the blood were confirmed. In the CPB Ext-oxy group, PLT counts were significantly preserved at 60 and 120 min after the start of circulation compared with those in the CPB Int-oxy group. However, no significant differences in IL-6, IL-10, or TNF-α levels were observed between the CPB groups. Incorporating the extraluminal flow oxygenator into a rat CPB model enables the simulation of CPB conditions that closely mimic those encountered in clinical CPB.

Cardiovascular events occur 20 years earlier in Sub-Saharan Africa compared to Europe. The risk factors for atherosclerosis differ between population groups and according to age. We compared the main correlates of carotid intima-media thickness (IMT, an index of atherosclerosis) in young and older adults of African ancestry. Hemodynamic (central and peripheral arterial pressures) and metabolic factors (lipids, glucose, glycated haemoglobin), smoking status and carotid IMT were determined in 573 adult Africans. In young (age<35years, n = 181) and middle-aged (35-59years, n = 231) adults, carotid IMT was associated with hemodynamic and metabolic cardiovascular risk factors on bivariate analyses. In older (age≥60years, n = 161) adults only hemodynamic factors were associated with carotid IMT. After adjustments for confounders, lipids were not associated with carotid IMT at any adult age. Carotid IMT was independently associated with backward wave pressure (Pb, p = 0.001) and age (p = 0.006) in young adults; with hemodynamics (central systolic blood pressure, p = 0.003; Pb, p = 0.02), age (p = 0.0002), body mass index (BMI, p = 0.005) and heart rate (p = 0.007) in middle-aged adults; and with Pb (p < 0.0001), male sex (p = 0.03), and HR (p = 0.04) in older adults. Increased carotid IMT was related to Pb in young (odds ratio [OR] = 1.233, p = 0.0003) and older (OR = 1.086, p = 0.0059) adults, and BMI (OR = 1.089, p = 0.0005) in middle-aged adults. Improvements in predictive performance for detecting increased carotid IMT were shown with Pb in young (p = 0.0032) and older (p = 0.0031) adults, and with BMI (p = 0.0004) in middle-aged adults. In conclusion, in African adults in Sub-Saharan Africa, carotid IMT is associated with hemodynamic factors, but not lipids. Moreover, in young adults, carotid IMT is primarily associated with hemodynamic factors.

Intraosseous access, the fastest access in emergencies, isexclusively used for delivering medications or fluids. The correlation between intraosseous and arterial pressures remains unclear. This study aimed to explore this correlation at baseline and in various clinical scenarios (e.g., different heart rates, arrhythmias, asystolic arrest, and CPR). In 11 male Yorkshire pigs (73.4 ± 5.9kg), femoral artery and tibial Intraosseous lines were placed under anesthesia. Pressures were recorded during hemodynamic interventions and cardiac arrest. Analyses included Pearson's r, Wilcoxon rank-sum test, and BVAR. Intraosseous pressure showed correlating pulsatility with arterial pressure, ranging from 9 to 71% of mean arterial pressure. Correlation was strong under normal conditions (r = 0.75-0.96, p < 0.001) and during CPR (r = 0.65-0.99, p < 0.001), weakened during asystole (r = 0.26 ± 0.46, p < 0.001), and wasdisrupted by epinephrine (r = 0.04, p < 0.001). Asystole was identifiable on intraosseous tracings. Intraosseous pressure effectively reflects circulatory activity and may aid in accurately identifying asystole with possible clinical implications for CPR.

Despite higher morbidity and mortality risks, parents of preterm infants miss postpartum visits more often than parents of full-term infants. Whether the introduction of telemedicine improved access to postpartum care among parents of infants in the neonatal intensive care unit (NICU) is unknown. We aimed to compare postpartum visit attendance and care comprehensiveness for NICU parents before and after the option of telemedicine.We conducted a retrospective cohort study of postpartum parents without a history of hypertension who gave birth <32 weeks at two Philadelphia hospitals. We compared care receipt before and after implementation of telemedicine (2019 and 2023, respectively). Individuals with hypertension were excluded due to eligibility for a remote, text-based blood pressure monitoring program during the study period. Through manual chart review, we ascertained postpartum visit attendance and documentation of three core care elements: depression screening, contraception counseling, and blood pressure measurement.The proportion of parents without postpartum visits was similar in 2019 (13/69, 18.8%) and in 2023 (7/45, 15.6%; p = 0.65). While telemedicine was not available in 2019, 42.1% (16/38) of postpartum visits in 2023 were conducted via telemedicine. In 2019 and 2023, the proportion of visits with missed depression screenings (10.7 vs. 0%, p = 0.08) and contraception counseling (0 vs. 18.4%, p = 0.001) were low. Missed blood pressure measurements increased significantly from 3.9% in 2019 to 36.8% in 2023 (p < 0.0001); all missed measurements were during telemedicine visits.Despite the availability of telemedicine, approximately one in six NICU parents of preterm infants did not attend a postpartum visit. While telemedicine accounted for over one-third of visits in 2023, it was associated with gaps in essential care, specifically blood pressure measurements. Given the benefits of early detection and treatment for postpartum preeclampsia, supplementing telemedicine visits with in-person blood pressure measurements in NICUs may be warranted. · Telemedicine did not change postpartum visit attendance for parents of NICU infants.. · Missed postpartum blood pressures increased significantly after adoption of telemedicine.. · NICU-based blood pressure monitoring may mitigate care gaps introduced by telemedicine visits..

Hypertension is a leading risk factor for negative health outcomes due to end-organ effects that include small vessel disease in the brain. Low-renin hypertension is understudied at the blood pressure (BP), microvascular, and mechanistic level, and in relation to biological sex. This study examined the effects of low-renin hypertension, produced by activation of the brain renin-angiotensin system in a deoxycorticosterone acetate (DOCA) salt model. C57BL/6J mice were treated with DOCA (or sham) and given tap H2O and H2O with 0.15 mol/L NaCl for 3 to 4 weeks followed by assessment of the microvasculature. Mean arterial pressure and BP variability were measured using radiotelemetry. Baseline and diurnal changes in mean arterial pressure, increases in mean arterial pressure, and BP variability during DOCA salt, were greater in male than female mice. Compared with sham treatment, endothelial function of cerebral arterioles in vivo was reduced by >70% by DOCA salt in males, dysfunction that could be reversed by local inhibition of AT1R (angiotensin II type 1 receptor), MR (mineralocorticoid receptor), or Rho kinase. DOCA salt increased arteriolar cross-sectional area and wall stiffness in male, but not female mice. In males (but not females), performance on a novel object recognition test was selectively impaired. Activation of the central renin-angiotensin system has sex-specific effects on BP, diurnal changes in BP, BP variability, arteriolar structure, and stiffness. Marked endothelial dysfunction was present in males (with several contributing mechanisms). These findings provide new insight into BP-related and small vessel disease-related phenotypes, mechanisms that contribute to endothelial dysfunction, and sex-specific differences in BP traits in a preclinical model of low-renin hypertension.

Device-based therapies may augment decongestion in acute decompensated heart failure. We investigated the efficacy and safety of prolonged mechanical superior vena cava occlusion using the preCARDIA system in a swine model of heart failure. Over 6h of preCARDIA activation, right- and left-sided filling pressures were significantly reduced. Plasma levels of the brain injury marker ubiquitin C-terminal hydrolase L1 and intracerebral arterial pressure were not significantly changed. Post-mortem evaluation did not identify gross cerebral or histologic injury. Future studies are needed to compare continuous versus cyclic preCARDIA activation and to further confirm the neurologic safety of sustained superior vena cava occlusion.

Portal hypertension (pH) is a major determinant of complications associated with chronic liver disease, and high-risk varices (HRV) require prophylactic intervention. Hepatic venous pressure gradient (HVPG) measurement is the gold standardfor assessment. However, it is invasive. This study examined the most reliable noninvasive biomarker for evaluating HVPG and diagnosing HRV. Seventy-eight patients with chronic liver disease (including 44 with cirrhosis) underwent HVPG measurement. Noninvasive markers including 7S domain of type IV collagen (4COL7S), Mac-2-binding protein glycosylation isomer (M2BPGi), liver stiffness, enhanced liver fibrosis (ELF) score, hyaluronic acid and type III procollagen peptide levels, aspartate aminotransferase-to-platelet ratio index, fibrosis-4 index, platelet count, von Willebrand factor (vWF), a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) activity, vWF-to-ADAMTS13 ratio, and vWF antigen-to-platelet ratio score were evaluated. In the receiver operating characteristic analyses, 4COL7S had the highest diagnostic accuracy for both clinically significant HRV, with a superior area under the receiver operating characteristic curve compared with the other markers. 4COL7S showed the strongest correlation with HVPG (r=0.713 and 95% confident interval: 0.617-0.84), outperforming M2BPGi and the ELF score. Vascular markers, such as the vWF antigen-to-platelet ratio and vWF-to-ADAMTS13 ratio, had additional but weaker predictive ability. However, 4COL7S remained the most consistent predictor across both variceal outcomes and HVPG. 4COL7S is the most reliable noninvasive biomarker for predicting HRV. Its superior diagnostic accuracy supports its use as a practical surrogate for HVPG and as a valuable tool in clinical risk stratification for variceal bleeding.

Objective.Calf blood pressure (CBP) plays an important role in various clinical applications, such as determining the appropriate cuff pressure for compression therapy and diagnosis of lower extremity vascular diseases, which necessitates the integration of built-in measurement methods within the device. This study aimed to investigate the differences in human CBP assessments resulting from the application of variousin vivoexternal compression strategies.Approach.An experimental procedure incorporating different compression strategies, specially the low-pressure-sustained mode, the slow-inflation (SI) mode and the slow-deflation (SD) mode, was conducted to capture the dynamic responses of the photoplethysmography (PPG) signal for CBP evaluation. Nineteen subjects, including 13 males and 6 females, participated in this experimental study. Feature points related to CBP were extracted from dynamic responses of the PPG signal and subjected to statistical analysis. A lumped parameter model of the human lower extremity was developed to assist in analyzing the biomechanical factors underlying these differences.Main results.The experimental results indicated that the dynamic behaviors of the PPG signal followed clear and consistent patterns, and the CBP value derived from the PPG signal in the SI mode was significantly higher than that obtained in the SD mode. Model simulation results showed that the differences in the evaluated values of the CBP between the SI and SD modes were caused by the different collapse processes of calf arteries and veins.Significance.This study could help understand the forced collapse process of blood vessels in the calf and inspire new ideas on CBP evaluation and personalized compression therapy.

Correlation between Arterial Partial Pressure of Oxygen (PaO2) post ECMO initiation and Outcomes in Veno-Arterial Extracorporeal Membrane Oxygenation (VA ECMO)-analysis from ECMO Society of India Registry

The systems regulating blood pressure and calcium-magnesium (Ca2+-Mg2+) homeostasis are increasingly recognized to have clinically relevant interactions, where alterations in one can lead to significant changes in the other. In this study, we developed a computational model integrating blood pressure regulation and Ca2+-Mg2+ homeostasis in a male rat. We simulated various conditions, including hypertension, Ca2+, Mg2+, and vitamin D3 deficiencies, and primary hyperparathyroidism. Simulations of hypertension, induced by various stimuli like increased renin or aldosterone secretion, demonstrated significant effects on parathyroid hormone (PTH), calcitriol, renal Ca2+/Mg2+ handling, and bone resorption. Dietary Ca2+, Mg2+, and vitamin D3 deficiencies was predicted to elevate mean arterial pressure, with Mg2+ deficiency having a stronger effect. Furthermore, the model predicted that primary hyperparathyroidism elevates PTH, Ca2+, and calcitriol, leading to increased mean arterial pressure and bone loss. Overall, this model provides valuable insights into the mechanistic links between blood pressure regulation and Ca2+-Mg2+ homeostasis, offering insights into clinical conditions like hypertension and hyperparathyroidism.

To evaluate for the first time a combination of novel colour Doppler ultrasound (CDUS), greyscale (GSUS) and oscillometric indices of angiopathy in patients with autoinflammatory syndromes (AIS). Further, to explore the associations between these markers and patient- and disease-related characteristics, as well as traditional cardiovascular (CV) risk factors. CDUS was used to assess arterial compliance markers, such as resistance index, pulsatility index (PI) and flow-velocity integral (FVI) in the common carotid artery (CCA) of AIS patients and healthy controls. Additionally, GSUS was employed to measure carotid intima-media thickness (cIMT), detect plaques and quantify total calcification surface. Oscillometry was utilized to evaluate aortic stiffness by carotid-femoral pulse wave velocity (cfPWV). Thirty-one patients with AIS and 62-matched (1:2) healthy controls were recruited. AIS patients exhibited higher CCA-PI [1.89 (0.46) vs 1.59 (0.32), P = 0.024] and peak systolic velocity (80.15 vs 64.95 cm/s, P = 0.003), compared with controls. Moreover, AIS patients not receiving biologic therapy demonstrated significantly higher cfPWV [6.99 (1.71) vs 5.86 (0.81) m/s, P = 0.001]. cfPWV and cIMT were predicted by age (cfPWV: rho = 0.573, P < 0.001; cIMT: rho = 0.675, P = 0.002), systolic arterial pressure (SAP) (cfPWV: r = 0.464, P = 0.009; cIMT: rho = 0.514, P = 0.029) and lymphadenopathy (cfPWV: eta = 0.373, P = 0.039). PI associated with nicotine (rho = 0.691, P = 0.008) and FVI (inversely) with SAP (rho = -0.522, v0.026). In the first CV surrogate marker study in AIS combining oscillometry and arterial US, patients exhibited increased carotid pulsatility and altered flow dynamics vs controls. Aortic stiffness was lower in patients receiving biologics and mainly predicted by traditional CV factors and lymphadenopathy. Angiopathy markers may reveal significant vascular abnormalities in AIS patients, improving CV screening and risk classification.

Pulmonary Arterial Pressure Monitoring of the Pulmonary Hemodynamics With Vericiguat in Heart Failure With Reduced Ejection Fraction.

The systems regulating blood pressure and calcium-magnesium (Ca2+-Mg2+) homeostasis are increasingly recognized to have clinically relevant interactions, where alterations in one can lead to significant changes in the other. In this study, we developed a computational model integrating blood pressure regulation and Ca2+-Mg2+ homeostasis in a male rat. We simulated various conditions, including hypertension, Ca2+, Mg2+, and vitamin D3 deficiencies, and primary hyperparathyroidism. Simulations of hypertension, induced by various stimuli like increased renin or aldosterone secretion, demonstrated significant effects on parathyroid hormone (PTH), calcitriol, renal Ca2+/Mg2+ handling, and bone resorption. Dietary Ca2+, Mg2+, and vitamin D3 deficiencies was predicted to elevate mean arterial pressure, with Mg2+ deficiency having a stronger effect. Furthermore, the model predicted that primary hyperparathyroidism elevates PTH, Ca2+, and calcitriol, leading to increased mean arterial pressure and bone loss. Overall, this model provides valuable insights into the mechanistic links between blood pressure regulation and Ca2+-Mg2+ homeostasis, offering insights into clinical conditions like hypertension and hyperparathyroidism.

To compare 24-hour ambulatory blood pressure (ABP) between women with polycystic ovary syndrome (PCOS) and ovulatory controls, and to explore potential anthropometric, hormonal, metabolic, and inflammatory correlates of ABP in women with PCOS. In this cross-sectional study, 50 women with PCOS (diagnosed by Rotterdam criteria) and 50 ovulatory controls underwent office and 24-hour ABP monitoring. Clinical, anthropometric, hormonal, metabolic, and inflammatory parameters were assessed. Between-group comparisons were adjusted for body mass index (BMI). LASSO regression was used to identify variables independently associated with ABP in the PCOS group. Women with PCOS showed significantly higher 24-hour and daytime mean arterial pressure and heart rate compared to controls, even after adjustment for BMI (p < 0.05). No differences were observed in nighttime ABP or office blood pressure (p > 0.05). PCOS participants exhibited a more adverse cardiometabolic profile, including higher BMI, waist circumference, insulin, HbA1c, triglycerides, creatinine, and TNF-alfa, along with lower estradiol and progesterone levels. In LASSO models, BMI emerged as the only consistent independent predictor of ABP across all periods. Additional predictors, such as HbA1c (nighttime mean BP), creatinine (daytime diastolic BP), and waist circumference (daytime systolic BP), were retained in specific models, while most hormonal, metabolic, and inflammatory markers were not associated with ABP in the PCOS group. In summary, women with PCOS exhibit higher 24-hour and daytime ABP compared to ovulatory controls, independently of BMI. Adiposity, as assessed by BMI, appears to be a key factor associated with ABP in this population. These findings highlight the importance of 24-hour ABP monitoring and weight management in the cardiovascular risk assessment and care of women with PCOS.

Endothelial mechanosensing is essential for controlling vascular tone. LRRC8A (leucine-rich repeat-containing protein 8A) was previously identified as a core subunit of the mechanoresponsive LRRC8 complex, functionally encoding the endothelial volume regulatory anion channel and regulating vascular function. This study aims to identify the molecular identity of the endothelial LRRC8 complex and its function in vascular reactivity and blood pressure control. We generated germline epitope-tagged Lrrc8a-3xFlag knock-in mice and endothelium-specific Lrrc8a-3xFlag overexpression mice to permit LRRC8A and LRRC8C immunoprecipitation and define LRRC8 subunit interactions. We combined in vivo and in vitro loss-of-function models, electrophysiology, immunoblotting, and pressure myography of third-order mesenteric arteries to examine the contributions of individual LRRC8A/B/C subunits to vascular function and underlying signaling pathways. The contributions of LRRC8C to blood pressure control in vivo were further assessed using the angiotensin-induced hypertension model in Lrrc8c knockout mice. Although all LRRC8A-E subunits are expressed in endothelium, co-immunoprecipitation revealed enrichment of LRRC8A/B/C, suggesting the existence of an endothelial LRRC8A/B/C heteromer. Lrrc8a/b/c depletion studies showed codependent expression of LRRC8A/B/C, but not LRRC8D. Only LRRC8A and LRRC8C deficiency impaired AKT and endothelial NO synthase phosphorylation, increased myogenic tone (2.2- and 1.9-fold increase, respectively), and reduced endothelial NO synthase-dependent vasodilation (45% and 61% reduction, respectively). Global Lrrc8c knockout mice phenocopied Lrrc8a knockouts and exhibited exacerbated angiotensin-induced hypertension, as evidenced by 15% increase in mean arterial pressure. LRRC8A/B/C form the endothelial LRRC8 heteromeric complex. LRRC8C is nonredundant in supporting endothelial AKT-endothelial NO synthase signaling, vascular relaxation, and resistance to hypertension.

Evaluation of the relationship between noise exposure and arterial blood pressure and lipid profile disorders in wood industry workers: a cross-sectional study.