endothelin-1 and Sleep-Apnea--Obstructive

The association between obstructive sleep apnea (OSA) and cancer is still debated and data are scarce regarding the link between OSA and breast cancer progression. Since conclusive epidemiological studies require large sample sizes and sufficient duration of exposure before incident cancer occurrence, basic science studies represent the most promising approach to appropriately address the topic. Here we assessed the impact of intermittent hypoxia (IH), the major hallmark of OSA, on the development of breast cancer and explored the specific involvement of the endothelin signaling pathway. Original in vitro and in vivo models were used where 3D-spheroids or cultures of murine 4T1 breast cancer cells were submitted to IH cycles, and nude NMRI mice, orthotopically implanted with 4T1 cells, were submitted to chronic IH exposure before and after implantation. The role of the endothelin-1 in promoting cancer cell development was investigated using the dual endothelin receptor antagonist, macitentan. In vitro exposure to IH significantly increased 4T1 cell proliferation and migration. Meta-analysis of 4 independent in vivo experiments showed that chronic IH exposure promoted tumor growth, assessed by caliper measurement (overall standardized mean difference: 1.00 [0.45-1.55], p < 0.001), bioluminescence imaging (1.65 [0.59-2.71]; p < 0.01) and tumor weight (0.86 [0.31-1.41], p < 0.01), and enhanced metastatic pulmonary expansion (0.77 [0.12-1.42]; p = 0.01). Both in vitro and in vivo tumor-promoting effects of IH were reversed by macitentan. Overall, these findings demonstrate that chronic intermittent hypoxia exposure promotes breast cancer growth and malignancy and that dual endothelin receptor blockade prevents intermittent hypoxia-induced tumor development.

Topics: Animals; Endothelin-1; Hypoxia; Mice; Neoplasms; Receptor, Endothelin A; Sleep Apnea, Obstructive

Obstructive sleep apnea (OSA) is related to endothelin-1 (ET-1). Continuous positive airway pressure (CPAP) is an effective therapy for OSA. However, the effectiveness of CPAP on ET-1 levels in patients with OSA yielded contradictory results. We conducted a meta-analysis to assess the effect of CPAP on ET-1 levels in OSA.. The Embase, and Cochrane Library and PubMed were searched before March, 2018. The overall effects were measured by the standardized mean difference (SMD) with a 95% confidence interval (CI). Ten studies were included and the meta-analysis was conducted using Stata 14.0.. 10 studies involving 375 patients were included in the meta-analysis. The result showed that there was a significant reduction in ET-1 levels in OSA patients before and after CPAP therapy (SMD = - 0.74, 95% CI = - 1.30 to - 0.17, z = 2.56, p = 0.01). Further, subgroup analysis demonstrated that Apnea-Hypopnea Index (AHI), CPAP therapy duration, and sample size also affected CPAP therapy.. Our meta-analysis indicated that CPAP treatment among OSA patients was significantly was related to a decrease in ET-1 levels. Further prospective long-term studies with a larger number of patients are needed to evaluate and clarify this issue.

Topics: Biomarkers; Continuous Positive Airway Pressure; Endothelin-1; Humans; Sleep Apnea, Obstructive

Type 2 diabetes (T2D) accounts for about 90% of all diabetes patients and incurs a heavy global public health burden. Up to 50% of T2D patients will eventually develop neuropathy as T2D progresses. Diabetic peripheral neuropathy (DPN) is a common diabetic complication and one of the main causes of increased morbidity and mortality of T2D patients. Obstructive sleep apnea (OSA) affects over 15% of the general population and is associated with a higher prevalence of T2D. Growing evidence also indicates that OSA is highly prevalent in T2D patients probably due to diabetic peripheral neuropathy. However, the interrelations among diabetic peripheral neuropathy, OSA, and T2D hitherto have not been clearly elucidated. Numerous molecular mechanisms have been documented that underlie diabetic peripheral neuropathy and OSA, including oxidative stress, inflammation, endothelin-1, vascular endothelial growth factor (VEGF), accumulation of advanced glycation end products, protein kinase C (PKC) signaling, poly ADP ribose polymerase (PARP), nitrosative stress, plasminogen activator inhibitor-1, and vitamin D deficiency. In this review, we seek to illuminate the relationships among T2D, diabetic peripheral neuropathy, and OSA and how they interact with one another. In addition, we summarize and explain the shared molecular mechanisms involved in diabetic peripheral neuropathy and OSA for further mechanistic investigations and novel therapeutic strategies for attenuating and preventing the development and progression of diabetic peripheral neuropathy and OSA in T2D.

Topics: Animals; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Disease Progression; Endothelin-1; Glycation End Products, Advanced; Humans; Mice; Neurotransmitter Agents; Oxidative Stress; Plasminogen Activator Inhibitor 1; Poly(ADP-ribose) Polymerases; Prevalence; Protein Kinase C; Rats; Sleep Apnea, Obstructive; Vascular Endothelial Growth Factor A

Obstructive sleep apnea (OSA) is now recognized as an independent and important risk factor for cardiovascular diseases such as hypertension, coronary heart disease, heart failure and stroke. Clinical and experimental data have confirmed that intermittent hypoxia is a major contributor to these deleterious consequences. The repetitive occurrence of hypoxia-reoxygenation sequences generates significant amounts of free radicals, particularly in moderate to severe OSA patients. Moreover, in addition to hypoxia, reactive oxygen species (ROS) are potential inducers of the hypoxia inducible transcription factor-1 (HIF-1) that promotes the transcription of numerous adaptive genes some of which being deleterious for the cardiovascular system, such as the endothelin-1 gene. This review will focus on the involvement of the ROS-HIF-1-endothelin signaling pathway in OSA and intermittent hypoxia and discuss current and potential therapeutic approaches targeting this pathway to treat or prevent cardiovascular disease in moderate to severe OSA patients.

Topics: Animals; Cardiovascular Diseases; Endothelin-1; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Reactive Oxygen Species; Risk Factors; Severity of Illness Index; Signal Transduction; Sleep Apnea, Obstructive

Topics: Animals; Endothelin-1; Gene Expression Regulation; Humans; Hypoxia; Hypoxia-Inducible Factor 1; NF-kappa B; Nitric Oxide; Oxidative Stress; Sleep Apnea, Obstructive; Vascular Endothelial Growth Factor A

Vascular endothelial dysfunction refers to a loss of normal homeostatic functions in the blood vessels. It is characterized by reduced vasodilation and enhanced vasoconstriction functions and chronic prothrombotic and inflammatory activity. There is convincing evidence for endothelial dysfunction in obstructive sleep apnea (OSA): OSA is associated with alterations in vascular structures and their elastic properties, increased circulating cell-derived microparticles, reduced endothelial repair capacity, and vascular reactivity. These alterations may be related to the reduced availability of nitric oxide, which has major vasoprotective effects including vasodilation, inhibition of platelet adhesion and aggregation, inhibition of leukocyte-endothelial adhesion and inhibition of smooth muscle cell proliferation. It is unknown whether endothelial dysfunction in OSA is due to alterations in vasoconstriction mechanisms related to angiotensin II or endothelin 1. In OSA, endothelial dysfunction may be related to chronic intermittent hypoxia and to sleep loss and fragmentation. These conditions may increase the levels of various markers of inflammation and oxidative stress, as well as those of increased procoagulant and thrombotic activity. In addition, they may produce an imbalance of vasomotor function. Endothelial dysfunction contributes to the development of atherosclerosis and cardiovascular disorders associated with OSA. However, other diseases that are also associated with endothelial dysfunction are OSA comorbidities, e.g. obesity, insulin resistance, smoking habits and cardiovascular diseases such as hypertension and coronary artery disease. This makes it difficult to demonstrate a causal link between OSA and endothelial dysfunction; nevertheless, evidence for such a link has been produced by therapeutic studies. The administration of continuous positive airway pressure may reverse changes associated with endothelial dysfunction and, therefore, may decrease the risk of cardiovascular disease in OSA patients.

Topics: Adult; Angiotensin II; Apoptosis; Biomarkers; Blood Coagulation Disorders; Cardiovascular Diseases; Continuous Positive Airway Pressure; Endothelin-1; Endothelium, Vascular; Humans; Nitric Oxide; Oxidative Stress; Risk Factors; Sleep Apnea, Obstructive

Obstructive Sleep Apnea Syndrome (OSAS) is a recognized risk factor for cardiovascular disorders and in some cases is complicated with Pulmonary Arterial Hypertension (PAH), as the endothelium is affected. Recent studies provide strong evidence for endothelial dysfunction in obstructive sleep apnea. The resultant vasoconstriction, abnormal cell proliferation and hyper-coagulability may lead to the initiation or progression of atherosclerotic cardiovascular and cerebrovascular disorders, which are frequently encountered in OSA patients. While the currently available therapies for OSAS, such as Continuous Positive Airway Pressure therapy (CPAP therapy), improve endothelial dysfunction, they are not well-tolerated by patients. CPAP therapy can reduce nocturnal hypoxemias and decrease noradrenaline circulating levels, but does not affect ET-1 plasma levels. Potent and selective Endothelin-1 receptor antagonists have been developed and have shown promising results in the treatment of cardiovascular diseases such as pulmonary arterial hypertension, acute and chronic heart failure, hypertension, renal failure, and atherosclerosis. However, results are often contrasting and complicated because of the tissue-specific vasoconstrictor actions of Endothelin-B receptors and the fact that endothelin is an autocrine and paracrine factor whose activity is difficult to measure in vivo.

Topics: Continuous Positive Airway Pressure; Endothelin-1; Humans; Hypertension, Pulmonary; Receptors, Endothelin; Sleep Apnea, Obstructive

1. The most usual form of chronic hypoxia in humans is the intermittent hypoxia resulting from obstructive sleep apnoea (OSA). The OSA syndrome is a highly prevalent sleep breathing disorder that is considered an independent risk factor for hypertension and cardiovascular diseases. Endothelial dysfunction, oxidative stress, inflammation and sympathetic activation have been proposed as potential mechanisms involved in the onset of the hypertension. However, evidence for a unique pathogenic mechanism has been difficult to establish in OSA patients because of concomitant comorbidities. Thus, animal models have been developed to study the pathological consequences of exposure to chronic intermittent hypoxia (CIH). 2. Because OSA patients and animals exposed to CIH show augmented ventilatory, sympathetic and cardiovascular responses to acute hypoxia, it has been proposed that enhanced carotid body responsiveness to hypoxia is involved in the autonomic changes induced by OSA and in the development of the hypertension. Recently, this proposal has received further support from recordings of carotid body chemosensory neural discharges in situ and in vitro showing that exposure of animals to CIH increases basal carotid body chemosensory discharges and enhances the chemosensory response to hypoxia. 3. In the present brief review, we discuss the evidence supporting an important role for the carotid body in the progression of cardiorespiratory changes induced by OSA and the contribution of oxidative stress, endothelin-1 and pro-inflammatory molecules in the potentiation of the carotid body chemosensory function induced by CIH.

Topics: Animals; Cardiovascular System; Carotid Body; Chemoreceptor Cells; Endothelin-1; Humans; Hypertension; Hypoxia; Inflammation Mediators; Models, Biological; Oxidative Stress; Respiratory Mechanics; Respiratory System; Sleep Apnea, Obstructive; Sympathetic Nervous System

Obstructive sleep apnea is a common disorder that is often unrecognized and underappreciated. Emerging evidence suggests that there is a causal link between obstructive sleep apnea and hypertension. This relationship appears to be independent of other comorbidities that have been previously linked to hypertension, such as obesity. The majority of studies support the contention that alleviation of sleep disordered breathing has a clinically significant beneficial impact on decreasing both nighttime and daytime blood pressure. A pathophysiologic basis for patients with sleep apnea having an increased risk for hypertension is not fully elucidated. However, there is consistent evidence that autonomic mechanisms are implicated. Sympathetic activation along with humoral responses to repetitive episodes of hypoxemia and apnea over the longer term may cause vasoconstriction, endothelial dysfunction, and possibly hypertension. Patients with sleep apnea are often obese and may be predisposed to weight gain. Hence, obesity may further contribute to hypertension in this patient population.

Topics: Blood Pressure; Endothelin-1; Female; Humans; Hypertension; Leptin; Male; Obesity; Positive-Pressure Respiration; Risk Factors; Sleep Apnea, Obstructive; Sympathetic Nervous System

Obstructive sleep apnoea (OSA) is associated with cardiovascular disease. Intermittent hypoxia, endothelial dysfunction and adipose tissue-mediated inflammation have all been linked to cardiovascular disease in OSA. We therefore explored the effect of OSA on relevant associated blood markers: adrenomedullin (ADM), endocan, endothelin-1 (ET-1), resistin and vascular endothelial growth factor (VEGF).. Patients with OSA, established on and compliant with continuous positive airways pressure (CPAP) therapy for >1 year were included from three randomized controlled trials, conducted at two centres. Patients were randomized to either continued therapeutic CPAP or sham CPAP (CPAP withdrawal) for 2 weeks. Blood markers were measured at baseline and at 14 days and the treatment effect between sham CPAP and therapeutic CPAP was analysed.. A total of 109 patients were studied (therapeutic CPAP n = 54, sham CPAP n = 55). Sham CPAP was associated with a return of OSA (between-group difference in oxygen desaturation index (ODI) 36.0/h, 95% CI 29.9-42.2, P < 0.001). Sham CPAP was associated with a reduction in ADM levels at 14 days (-26.0 pg/mL, 95% CI -47.8 to -4.3, P = 0.02), compared to therapeutic CPAP. Return of OSA was not associated with changes in endocan, ET-1, resistin or VEGF.. Whilst CPAP withdrawal was associated with return of OSA, it was associated with an unexpected significant reduction in the vasodilator ADM and not with expected increases in hypoxia-induced markers, markers of endothelial function or resistin. We propose that the vascular effects occurring in OSA may be brought about by other mechanisms, perhaps partly through a reduction in ADM.

Topics: Adrenomedullin; Adult; Aged; Biomarkers; Continuous Positive Airway Pressure; Endothelin-1; Female; Humans; Hypoxia; Inflammation; Male; Middle Aged; Neoplasm Proteins; Patient Compliance; Proteoglycans; Resistin; Sleep Apnea, Obstructive; Vascular Endothelial Growth Factor A; Ventilator Weaning

This study aimed to examine the effects of carbocysteine in OSAS patients.. A total of 40 patients with moderate to severe obstructive sleep apnea syndrome (OSAS) were randomly divided into two groups. One group was treated with 1500 mg carbocysteine daily, and the other was treated with continuous positive airway pressure (CPAP) at night. Before treatment and after 6 weeks of treatment, all patients underwent polysomnography and completed questionnaires. Treatment compliance was compared between the two groups. Plasma was collected for various biochemical analyses. Endothelial function was assessed with ultrasound in the carbocysteine group.. The proportion of patients who fulfilled the criteria for good compliance was higher in the carbocysteine group (n = 17) than in the CPAP group (n = 11; 100% vs. 64.7%). Compared with baseline values, the carbocysteine group showed significant improvement in their Epworth Sleepiness Scale score (10.18 ± 4.28 vs. 6.82 ± 3.66; P ≤ 0.01), apnea-hypopnea index (55.34 ± 25.03 vs. 47.56 ± 27.32; P ≤ 0.01), time and percentage of 90% oxygen desaturation (12.66 (2.81; 50.01) vs. 8.9 (1.41; 39.71); P ≤ 0.01), and lowest oxygen saturation level (65.88 ± 14.86 vs. 70.41 ± 14.34; P ≤ 0.01). Similar changes were also observed in the CPAP group. The CPAP group also showed a decreased oxygen desaturation index and a significant increase in the mean oxygen saturation after treatment, but these increases were not observed in the carbocysteine group. Snoring volume parameters, such as the power spectral density, were significantly reduced in both groups after the treatments. The plasma malondialdehyde level decreased and the superoxide dismutase and nitric oxide levels increased in both groups. The endothelin-1 level decreased in the CPAP group but did not significantly change in the carbocysteine group. Ultrasonography showed that the intima-media thickness decreased (0.71 ± 0.15 vs. 0.66 ± 0.15; P ≤ 0.05) but that flow-mediated dilation did not significantly change in the carbocysteine group.. Oral carbocysteine slightly improves sleep disorders by attenuating oxidative stress in patients with moderate to severe OSAS. Carbocysteine may have a role in the treatment of OSAS patients with poor compliance with CPAP treatment. However, the efficiency and feasibility of carbocysteine treatment for OSAS needs further evaluation.. ClinicalTrials.gov NCT02015598.

Topics: Adult; Antioxidants; Carbocysteine; Carotid Intima-Media Thickness; Continuous Positive Airway Pressure; Endothelin-1; Humans; Male; Malondialdehyde; Middle Aged; Nitric Oxide; Oxygen; Polysomnography; Sleep Apnea, Obstructive; Snoring; Superoxide Dismutase

Obstructive sleep apnoea (OSA) is a risk factor for cardiovascular morbidity and mortality. The mechanism is unknown, but endothelial dysfunction might contribute. We tested the hypothesis that patients with OSA have abnormal nitric oxide (NO) synthesis, which results in an abnormal response in blood pressure, renal hemodynamics, renal tubular function and vasoactive hormones in response to inhibition of the NO synthesis with L-NMMA.. A randomized, placebo-controlled, single-blinded, crossover study was done in 13 OSA patients and 14 controls. We measured changes in systolic and diastolic blood pressure (SBP and DBP), pulse rate, glomerular filtration rate, renal plasma flow, fractional excretion of sodium and lithium and plasma concentrations of vasoactive hormones after injection of L-NMMA and placebo.. L-NMMA induced a significant increase in SBP and DBP in both groups. The placebo-corrected increase in DBP was more pronounced in patients with OSA than in controls (9 (5-11) versus 3 (1-6) mmHg; p=0.01). Endothelin-1 (ET-1) was significantly higher in patients compared with controls (1.1 (1.0-1.3) versus 0.8 (0.7-0.9) pg/mL; p<0.01). In controls, L-NMMA induced a small increase in ET-1, while no changes were seen in patients. The placebo-corrected change in ET-1 was lower in patients compared to controls (-01 (-0.3-0.0) versus 0.1 (0.0-0.1) pg/mL; p=0.04).. Patients with OSA have abnormally increased NO synthesis and an increased unresponsive level of ET-1 in plasma. This might be due to an imbalance between NO synthesis and ET-1 production.

Topics: Adult; Aged; Blood Pressure; Endothelin-1; Female; Heart Rate; Humans; Male; Middle Aged; NG-Nitroarginine Methyl Ester; Nitric Oxide; Renal Circulation; Sleep Apnea, Obstructive

To study the association between the indices of endothelial function in obstruction sleep apnea-hypopnea syndrome (OSAHS) and coronary heart disease (CHD) and the effect of nasal continuous positive airway pressure (nCPAP) on the combination of OSAHS and CHD.. A total of 80 subjects were prospectively recruited into four groups including control, OSAHS, CHD, OSAHS with CHD groups, with 20 subjects each. The indices of sleep apnea, serum nitric oxide (NO), and plasma endothelial-1 (ET-1) were measured. The changes of concentration of ET-1 and NO were compared before and after nCPAP therapy. The associations between ET-1 and NO and MSpO2, CT90 were analyzed.. (1) Multi-variable logistic analysis showed that OSAHS was one of the risk factors for CHD (OR = 0.511). (2) Compared with the control subjects and CHD group, there were significantly higher values of CT90, concentrations of ET-1 and lower values of MSpO2, concentrations of NO in both OSAHS and OSAHS with CHD groups (P < 0.01). There were no significant difference in sleep apnea indices between OSAHS and OSAHS with CHD groups (P > 0.05). However, in the group of OSAHS with CHD, the plasma ET-1 was significantly higher, whereas the serum NO was significantly lower than that in the group of OSAHS alone (P < 0.01). (3) The concentration of serum NO in the group of OSAHS was positively correlated with MSpO2 (r = 0.519, P < 0.05) and inversely correlated with CT90 (r = -0.529, P < 0.05). In addition, the concentration of plasma ET-1 was inversely correlated with MSpO2 (r = -0.457, P < 0.05) and positively correlated with CT90 (r = 0.476, P < 0.05). (4) In the groups of OSAHS and OSAHS with CHD, MSpO2, NO and NO/ET-1 after nCPAP therapy were higher than those before therapy, while CT90 and ET-1 were lower than those before therapy (P < 0.01).. OSAHS is one of the risk factors for CHD. Endothelial function was significantly impaired in OSAHS patients, and more severe in patients with OSAHS with CHD. The impairment of endothelial function may be one of the main mechanisms for the development or deterioration of CHD in OSAHS patients. The vascular endothelial dysfunction can be ameliorated by nCPAP treatment, which is correlated with improvement of nocturnal hypoxemia.

Topics: Adult; Body Weight; Continuous Positive Airway Pressure; Coronary Disease; Endothelin-1; Endothelium, Vascular; Female; Humans; Logistic Models; Male; Middle Aged; Nitric Oxide; Sleep Apnea, Obstructive

An association has been suggested between acute myocardial infarction (AMI) and obstructive sleep apnea (OSA). Considering the role of adipose-tissue-derived inflammatory mediators (adipokines) and the shared risk factor of obesity in OSA and AMI, this study aimed to investigate the involvement of adipokines in AMI patients with and without OSA. Serum levels of adipokines and inflammatory mediators were quantified, and home respiratory polygraphy was conducted. A total of 30 AMI patients and 25 controls were included. Patients with AMI exhibited elevated levels of resistin (7.4 vs. 3.7 ng/mL), interleukin-6 (8.8 vs. 1.3 pg/mL), and endothelin-1 (3.31 vs. 1.8 pg/mL). Remarkably, AMI patients with concomitant OSA exhibited higher levels of resistin (7.1 vs. 3.7 ng/mL), interleukin-6 (8.9 vs. 1.3 pg/mL), endothelin-1 (3.2 vs. 1.8 pg/mL), creatin kinase (1430 vs. 377 U/L), creatine kinase-MB (64.6 vs. 9.7 ng/mL), and troponin T (2298 vs. 356 pg/mL) than their non-OSA counterparts. Leptin showed a correlation with OSA severity markers. OSA was associated with greater cardiac damage in AMI patients. Our findings underscore that adipokines alone are not sufficient to discriminate the risk of AMI in the presence of OSA. Further research is necessary to determine the potential mechanisms contributing to exacerbated cardiac damage in patients with both conditions.

Topics: Adipokines; Endothelin-1; Humans; Inflammation Mediators; Interleukin-6; Myocardial Infarction; Resistin; Sleep Apnea, Obstructive

Hypertension occurred in 50% obstructive sleep apnea-hypopnea syndrome (OSAHS) patients meanwhile OSAHS occurred in 30% hypertension patients. The present study aimed to explore the molecular mechanism of GATA2-EDN1-AGT induced hypertension in the development of obstructive sleep apnea-hypopnea syndrome. OSAHS patients (56 cases: 36 cases of male, 20 cases of female, 42~60 years old) were divided into two groups (case group: patients with hypertension monitored by 24 h ambulatory blood pressure and polysomnography; control group: patients without hypertension). Wistar rats were used to establish the OSAHS model (narrow pharyngeal cavity). PaO2 and PaCO2 of patients and rats were measured by an automatic blood gas analyzer. The profile of total protein in the OSAHS group and normal group was evaluated. Protein-protein-interaction (PPI) was carried out to show all matter proteins related. The levels of EDN-1, AGTII and atrial natriuretic peptide (ANP) in blood samples of patients and rats were analyzed by enzyme-linked immunosorbent assay (ELISA). The expression of GATA2, EDN1, endothelin-converting enzyme 1 (ECE-1) and AGTⅡ was measured. The results showed that SaO2 and AHI were positively associated with systolic pressure (P<0.05) in OSAHS patients. There was no correlation among other indexes (P>0.05). It was also observed that GATA2 had a strong relationship with AGTⅡ and EDN1. The results of ELISA presented that the levels of EDN1, AGTⅡ and ANP in the OSAHS group of human and animal models were significantly increased (P<0.05). The results of immunochemistry showed that the expression of GATA2 and AGTⅡ in the vascular of OSAHS group was upregulated manifestly (P<0.05). It was concluded that OSAHS can induce AHI, which increases hypertension via the GATA2-EDN1-AGT Ⅱ axis.

Topics: Angiotensinogen; Animals; Atrial Natriuretic Factor; Blood Pressure Monitoring, Ambulatory; Endothelin-1; Female; GATA2 Transcription Factor; Hypertension; Male; Rats; Rats, Wistar; Sleep Apnea, Obstructive; Syndrome

Adropin is a recently discovered peptide hormone that plays a vital role in metabolism and cardiovascular-cerebrovascular function. The purpose of this study is to investigate the role of circulating adropin levels in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and further determine the relationship between serum adropin concentration and endothelial dysfunction in patients with OSAHS.. Forty polysomnography-diagnosed patients with OSAHS and 21 age and sex-matched healthy controls were enrolled in the current study. Serum adropin level, endothelial function parameters including flow-mediated dilatation (FMD) of brachial artery, endothelin-1 (ET-1), and nitric oxide (NO) were measured in all participants.. Serum adropin levels were significantly lower in patients with OSAHS compared to the control subjects. FMD was lower and serum ET-1 levels were higher in patients with OSAHS compared to control subjects. No significant difference was seen in serum NO levels between the two groups. Multivariate linear regression analysis revealed that serum adropin level was positively associated with FMD and negatively correlated with AHI. Additionally, serum adropin levels were lower in patients with OSAHS who had endothelial dysfunction compared with those patients without endothelial dysfunction. The receiver operating characteristic (ROC) analysis showed that area under the curve (AUC) for serum adropin in predicting endothelial dysfunction status in patients with OSAHS was 0.815 (95% CI 0.680-0.951, p = 0.001). The cutoff value of serum adropin level was less than 235.0 pg/mL, which provided the sensitivity and specificity of 81% and 75%, respectively, for the detection of endothelial dysfunction in patients with OSAHS.. Lower circulating adropin levels are closely associated with endothelial dysfunction in patients with OSAHS. Circulating adropin level may serve as an early biomarker to predict the development of endothelial dysfunction before the emergence of clinical symptoms in patients with OSAHS.

Topics: Adult; Biomarkers; Endothelin-1; Endothelium, Vascular; Female; Humans; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Nitric Oxide; Sleep Apnea, Obstructive

The search of biochemical markers of endothelial dysfunction: lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)-involved in atherosclerotic plaques formation-and endothelin-1 (ET-1)-potent vasoconstrictor-might help in detecting obstructive sleep apnea (OSA) patients at high risk of cardiovascular diseases.. In 71 OSA patients (apnoea/hypopnoea index, AHI 28.2 ± 17.9/hour) and in 21 healthy controls the serum levels of LOX-1 and ET-1 were measured.. There were increased levels of ET-1 (1.58 ± 0.65 vs. 1.09 ± 0.38 pg/mL;. There is endothelial dysfunction in OSA patients as indicated by increased serum levels of ET-1 and possibly endothelial dysfunction in diabetic OSA patients as indicated by increased serum levels of LOX-1 and its correlation with fasting glucose levels.

Topics: Biomarkers; Cardiovascular Diseases; Endothelin-1; Humans; Scavenger Receptors, Class E; Sleep Apnea, Obstructive

Both obstructive sleep apnea (OSA) and (at least a fraction of) sudden infant death syndrome (SIDS) are associated with impaired respiration. For OSA, an association with several gene variants was identified. Therefore, our hypothesis is that these polymorphisms might be of relevance in SIDS as well.. Twenty-four single nucleotide polymorphisms (SNPs) in 21 candidate genes connected to OSA, were genotyped in a total of 282 SIDS cases and 374 controls. Additionally, subgroups based on factors codetermining the SIDS risk (age, sex, season, and prone position) were established and compared as well.. Two of the analyzed SNPs showed nominally significant differences between SIDS and control groups: rs1042714 in ADRB2 (adrenoceptor beta 2) and rs1800541 in EDN1 (endothelin 1). In the subgroup analyses, 10 further SNPs gave significant results. Nevertheless, these associations did not survive adjustment for multiple testing.. Our results suggest that there might be a link between SIDS and OSA and its resulting respiratory and cardiovascular problems, albeit this predisposition might be dependent on the combination with other, hitherto unknown gene variants. These findings may encourage replication studies to get a better understanding of this connection.

Topics: Case-Control Studies; Endothelin-1; Female; Genetic Predisposition to Disease; Genotype; Germany; Humans; Infant; Infant, Newborn; Male; Polymorphism, Single Nucleotide; Receptors, Adrenergic, beta-2; Sleep Apnea, Obstructive; Sudden Infant Death

Although considerable research highlights the interactions between obstructive sleep apnea-hypopnea syndrome (OSAHS) and cardiovascular diseases, the effect of mandibular advancement device (MAD) treatment on cardiovascular complications in OSAHS patients remains unclear. We evaluated the effect of OSAHS treatment with MADs on the myocardium. All methods in this study were in accordance with relevant guidelines and regulations of the medical ethics committee in Hospital of Stomatology, Hebei Medical University approved the work. Thirty New Zealand rabbits were randomized into three groups: the control group, Group OSAHS, and Group MAD. Hydrophilic polyacrylamide gel was injected into the soft palate of the rabbits to induce OSAHS. In Group MAD, a MAD was positioned after OSAHS induction. All animals were induced to sleep in a supine position for 4-6 h/day for 8 weeks. Echocardiography was used to determine the structure and function of the heart. The histological changes were detected by optical microscopy and transmission electron microscopy (TEM). The levels of ET-1(endothelin-1) and Ang II (Angiotensin II) in the plasma were measured by an enzyme-linked immunosorbent assay (ELISA). The expression of ET-1 mRNA in heart tissue was detected by RT-PCR. Histological abnormalities, left ventricular hypertrophy, and left ventricular dysfunctions were demonstrated in Group OSAHS, and the abnormities were rescued with MAD treatment. Higher levels of plasma ET-1 and Ang II and elevated expression of ET-1 mRNA in cardiac tissue were detected in Group OSAHS compared with Group MAD and the control group. The blood oxygen saturation was negatively correlated with the levels of ET-1 and Ang II. OSAHS-induced elevated levels of ET-1 and Ang II may be attributed to myocardial structural abnormalities and dysfunction. Early treatment of MADs may play an important role in preventing myocardial damage in OSAHS rabbit model.

Topics: Acrylic Resins; Angiotensin II; Animals; Cytokines; Echocardiography; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Heart; Male; Myocardium; Occlusal Splints; Polysomnography; Rabbits; RNA, Messenger; Sleep Apnea, Obstructive; Ventricular Dysfunction, Left

Topics: Aged; Benzofurans; Continuous Positive Airway Pressure; Endothelin-1; Humans; Neuroprotective Agents; Nitric Oxide; Sleep Apnea, Obstructive

Background Obstructive sleep apnoea (OSA) is an independent risk factor of hypertension and cardiovascular diseases. Recurrent episodes of upper airways collapse during sleep causing blood oxygen desaturation, hypercapnia, and micro-arousals, are known to activate the sympathetic nervous system (SNS). However, whether changes in the renin-angiotensin-aldosterone system and endothelial activation also occur remains contentious. Methods Based on routine use of drug-induced sleep endoscopy (DISE) for the work-up of OSA patients in our centre, we designed a prospective study to investigate the haemodynamic and humoral changes occurring during the apnoeic episodes reproduced in vivo in the course of DISE. Specifically, plasma aldosterone concentration and renin activity, C-terminal fragment of proendothelin-1, as a marker of endothelial damage, and free plasma catecholamines, will be measured at fixed times during DISE. The activity of catechol-O-methyltransferase (COMT), a key catecholamine-inactivating enzyme that has been scantly investigated thus far owing to the lack of commercially available kits, will be also determined by a newly developed high performance liquid chromatography method, which is herein described. Results and conclusions The aim of this study is to provide novel information on the haemodynamic, hormonal, and SNS changes, and also on COMT activity modification concomitantly occurring during apnoea, thus contributing substantively to the understanding of the pathophysiology of OSA.

Topics: Adult; Aldosterone; Catechol O-Methyltransferase; Catecholamines; Endoscopy; Endothelin-1; Humans; Male; Pilot Projects; Prospective Studies; Protein Precursors; Renin; Research Design; Sleep; Sleep Apnea, Obstructive

The purpose of this study was to elucidate the role of microRNA-130a (miR-130a) in obstructive sleep apnea hypopnea syndrome (OSAHS)-associated pulmonary hypertension (PHT) by targeting the growth arrest-specific homeobox (GAX) gene.. A total of 108 patients with OSAHS-associated PHT were recruited as the OSAHS-associated PHT group and 110 healthy individuals were randomly selected as the normal control group. Human umbilical vein endothelial cells (HUVECs) were selected and divided into the control, miR-130a mimic, mimic negative control (NC), miR-130a inhibitor, and inhibitor-NC groups. The dual luciferase reporter gene assay was used to identify the relationship between miR-130a and the GAX gene. The quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were applied for the relative expressions of miR-130a and the mRNA and protein expressions of GAX. Serum levels of endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), nitric oxide (NO), and super oxide dismutase (SOD) were detected. Cell apoptosis and angiogenic activity were analyzed by flow cytometry and cell tube formation assay.. GAX was a target gene of miR-130a. Compared with the normal control group, the relative expression of miR-130a and the serum levels of ET-1 and VEGF were increased, whereas the mRNA expression of GAX and the serum levels of NO and SOD were decreased in the OSAHS-associated PHT group. Compared with the control, mimic-NC, and inhibitor-NC groups, the relative expressions of miR-130a in the miR-130a mimic group were enhanced, whereas the expression of miR-130a in the miR-130a inhibitor group was reduced. However, the mRNA and protein expressions of GAX showed an opposite trend in the miR-130a mimic and miR-130a inhibitor groups. In comparison to the control, mimic-NC, and inhibitor-NC groups, the miR-130a mimic group had an increase of ET-1 and VEGF expressions, whereas the expressions of NO and SOD were reduced. However, the miR-130a inhibitor group exhibited an opposite trend. The apoptosis rate and tube formation number in the miR-130a mimic group were obviously increased, whereas the miR-130a inhibitor group showed an obvious decrease.. These data provided strong evidence that miR-130a may be involved in the progression of OSAHS-associated PHT by down-regulating GAX gene.

Topics: Apoptosis; Biomarkers; Cells, Cultured; Down-Regulation; Endothelin-1; Female; Homeodomain Proteins; Human Umbilical Vein Endothelial Cells; Humans; Hypertension, Pulmonary; Male; MicroRNAs; Middle Aged; Nitric Oxide; Random Allocation; RNA, Messenger; Sleep Apnea, Obstructive; Superoxide Dismutase; Transfection; Vascular Endothelial Growth Factor A

The aim of the study was to evaluate exhaled nitric oxide (eNO) derived from different areas of airway in obstructive sleep apnea hypopnea syndrome (OSAHS) patients with NO exchange model and investigate the potential application and interpretation of eNO in clinical setting.. This study was divided into two parts. Firstly, we performed a case control study in 32 OSAHS patients and 27 non-OSAHS participants. Fractional eNO (FeNO) and eNO from the central airway (J'awNO) and from alveoli (CANO) were compared in OSAHS and control groups. Also, correlation of eNO to severity of OSAHS was analyzed. Secondly, a prospective study was conducted in 30 severe OSAHS patients who received a short-term nasal continuous positive airway pressure (nCPAP) treatment. We evaluated eNO, plasma ET-1 concentration, and echocardiography during the treatment process and explored the potential relationship among them.. FeNO and J'awNO were higher in OSAHS and associated with disease severity, while CANO was relatively lower. After nCPAP treatment in severe OSAHS patients, FeNO and J'awNO decreased and CANO increased significantly. Substantial agreement was shown between the elevation of CANO and the decrease of plasma ET-1 concentration after nCPAP by Kappa analysis for consistency. Tei index, which is considered indicative of global right ventricular function, might be predicted by plasma ET-1 levels in severe OSAHS patients.. NO exchange model provides us with more information of eNO derived from different areas. eNO is not only confirmed to be an effective method for airway inflammation evaluation in the follow-up of OSAHS, CANO may also serve as a useful marker in monitoring endothelial function, resistance of pulmonary circulation, and right ventricular function for clinical implication.

Topics: Breath Tests; Bronchi; Cardiovascular Diseases; Case-Control Studies; Comorbidity; Continuous Positive Airway Pressure; Endothelin-1; Endothelium; Exhalation; Female; Humans; Male; Middle Aged; Nitric Oxide; Pulmonary Alveoli; Reference Values; Sleep Apnea, Obstructive; Statistics as Topic; Ventricular Function, Right

Obstructive sleep apnea (OSA) and obesity are increasingly prevalent worldwide. Both promote endothelial dysfunction contributing to systemic and pulmonary hypertension over time. Endothelin-1 (ET-1) plays a pivotal role in the development of pulmonary hypertension (PH). The aim of the present study was to assess the association between plasma ET-1 and echocardiographic findings in obese individuals with and without OSA, as well as in non-obese patients with OSA.. Ninety-seven subjects (56 males) were enrolled in the study. All subjects underwent the following tests: venous endothelin-1 levels, pulmonary function testing, and arterial blood gas analysis. All patients except controls underwent transthoracic echocardiography and portable testing for sleep-disordered breathing.. Plasma ET-1 levels were significantly higher in obese patients, both with and without OSA (respectively, n = 30 (mean value, 268.06 ± 49.56 pg/ml) and n = 32 (mean value, 263.12 ± 65.26 pg/ml)), compared with non-obese patients with OSA or to healthy controls (respectively, n = 20 (mean value, 149.8 ± 23.09 pg/ml) and n = 15 (mean value, 152.3 ± 27.64 pg/ml); p < 0.0001). Pulmonary artery pressure (PAPs) in obese patients with OSA were significantly higher than in obese patients without OSA (p < 0.0001), while there was no statistical difference between PAPs of obese patients without OSA, compared with the group of non-obese OSA patients. Plasma ET-1 levels significantly correlated with systolic PAPs in obese patients both with and without OSA (respectively, n = 30, r = 0.385, p = 0.03567; n = 32, r = 0.3497, p = 0.0497).. Our study suggests that endothelin levels are more strongly associated with weight than the presence of sleep-disordered breathing, but pulmonary artery hypertension is associated with both weight and OSA.

Topics: Adult; Comorbidity; Echocardiography, Doppler; Endothelin-1; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Obesity; Polysomnography; Pulmonary Wedge Pressure; Reference Values; Sleep Apnea, Obstructive; Statistics as Topic

Obstructive sleep apnea (OSA) is a major risk factor for cardiovascular mortality, and apnea-induced intermittent hypoxia (IH) is known to promote various cardiovascular alterations such as vascular remodeling. However, the mechanisms that underlie IH remain incompletely investigated. We previously demonstrated that the hypoxia-inducible factor-1 (HIF-1) and endothelin-1 (ET-1) are involved in arterial hypertension and myocardial susceptibility to infarction induced by IH. Thus the objective of the present study was to investigate whether both ET-1 and HIF-1 were also involved in the vascular inflammatory remodeling induced by IH. Mice partially deficient for the Hif1α gene (HIF-1α(+/-)) and their wild-type equivalents, as well as C57BL/6J mice, treated or not with bosentan, a dual endothelin receptor antagonist, were exposed to IH or normoxia for 2 wk, 8 h/day. Splenocyte proliferative and secretory capacities, aortic nuclear factor-κB (NF-κB) and HIF-1 activities, and expression of cytokines and intima-media thickness (IMT) were measured. IH induced a systemic and aortic inflammation characterized by an increase in splenocyte proliferative and secretory capacities, aortic NF-κB activity, and cytokine expression in the aortic wall. This was accompanied by an increase in IMT. These modifications were prevented in HIF-1α(+/-) and bosentan-treated mice. The results of this study suggest that ET-1 is a major contributor to the vascular inflammatory remodeling induced by OSA-related IH, probably through HIF-1-dependent activation of NF-κB.

Topics: Animals; Aorta; Carotid Intima-Media Thickness; Cytokines; Endothelin-1; Hypertension; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Mice; Mice, Inbred C57BL; NF-kappa B; Sleep Apnea, Obstructive; Vascular Remodeling

Topics: Biomarkers; Endothelin-1; Heart Failure; Humans; Polysomnography; Sleep Apnea, Obstructive

Obstructive sleep apnea (OSA) is associated with cerebrovascular diseases. However, little is known regarding the effects of OSA on the cerebrovascular wall. We tested the hypothesis that OSA augments endothelin-1 (ET-1) constrictions of cerebral arteries. Repeated apneas (30 or 60 per hour) were produced in rats during the sleep cycle (8 hours) by remotely inflating a balloon implanted in the trachea. Four weeks of apneas produced a 23-fold increase in ET-1 sensitivity in isolated and pressurized posterior cerebral arteries (PCAs) compared with PCAs from sham-operated rats (EC50=10(-9.2) mol/L versus 10(-10.6) mol/L; P<0.001). This increased sensitivity was abolished by the ET-B receptor antagonist, BQ-788. Constrictions to the ET-B receptor agonist, IRL-1620, were greater in PCAs from rats after 2 or 4 weeks of apneas compared with that from sham-operated rats (P=0.013). Increased IRL-1620 constrictions in PCAs from OSA rats were normalized with the transient receptor potential channel (TRPC) blocker, SKF96365, or the Rho kinase (ROCK) inhibitor, Y27632. These data show that OSA increases the sensitivity of PCAs to ET-1 through enhanced ET-B activity, and enhanced activity of TRPCs and ROCK. We conclude that enhanced ET-1 signaling is part of a pathologic mechanism associated with adverse cerebrovascular outcomes of OSA.

Topics: Animals; Blotting, Western; Cerebrovascular Circulation; Disease Models, Animal; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Immunohistochemistry; Rats; Real-Time Polymerase Chain Reaction; Receptors, Endothelin; Signal Transduction; Sleep Apnea, Obstructive; Vasoconstriction

To evaluate the association of obstructive sleep apnea hypopnea syndrome (OSAHS) with carotid atherosclerosis and the efficacy of continuous positive airway pressure (CPAP) treatment.. A total of 93 OSAHS patients diagnosed by polysomnography (PSG) were selected from Sleep Disorders Center at Affiliated Hospital of Xuzhou Medical College between March 2013 and December 2014. Based on the results of apnea-hypopnea index (AHI), they were divided into mild (n=22), moderate (n=37), and severe OSAHS group (n=34). Meanwhile, 28 healthy adult individuals matched for age and body mass index (BMI) were enrolled as the control group. The carotid intima-mesa thickness (IMT) was measured by color Doppler uhrasonography, and plasma levels of tumor necrosis factor-α (TNF-α), endothelin-1 (ET-1) and nitric oxide (NO) were determined by Enzyme-Linked Immunosorbent Assay (ELISA). The correlations between carotid IMT and plasma levels of TNF-α, ET-1 and NO were analyzed. A total of 24 patients with moderate to severe OSAHS underwent CPAP treatment and the carotid IMT, plasma levels of TNF-α, ET-1 and NO were compared before and after CPAP treatment.. OSAHS patients had significant increase of carotid IMT with the increasing disease severity, and the carotid IMT in mild, moderate and severe OSAHS groups were all significantly higher than that in the control group ((0.73 ± 0.31), (0.86 ± 0.07), (1.07 ± 0.14) vs (0.65 ± 0.10) mm, all P<0.05). The plasma levels of TNF-α and ET-1 in mild to severe OSAHS group were significantly higher than those in controls ((17.45 ± 3.02), (23.81 ± 2.91), (35.16 ± 3.43) vs (12.53 ± 3.48) ng/L and (0.81 ± 0.13), (1.06 ± 0.21), (1.66 ± 0.30) vs (0.64 ± 0.12) ng/L, all P<0.05 ), whereas plasma levels of NO in the three OSAHS groups were significantly decreased compared with the control group ((35.46 ± 10.12), (29.32 ± 9.47), (20.16 ± 7.41) vs (45.43 ± 7.92) µmol/L, all P<0.05). Furthermore, there were significant differences in plasma levels of TNF-α, ET-1 and NO among the three OSAHS groups (all P<0.05). Carotid IMT was positively correlated with plasma TNF-α and ET-1 (r=0.56 and 0.51) and negatively correlated with plasma NO (r=-0.46) (all P<0.05). After 3 months of CPAP treatment, plasma levels of TNF-α and ET-1 in OSAHS patients were significantly reduced ((19.64 ± 5.28), (0.94 ± 0.21) vs (28.72 ± 5.36), (1.36 ± 0.36) ng/L), and plasma NO was markedly increased ((33.57 ± 6.32) vs (24.34 ± 4.46) µmol/L, all P<0.05). However, CPAP treatment did not have a significant effect on carotid IMT ((0.91 ± 0.21) vs (0.96 ± 0.14) mm), P>0.05).. Systemic inflammation and vascular endothelial dysfunction may play an important role in pathogenesis and development of carotid artery atherosclerosis in OSAHS. Short-term CPAP therapy alleviates systemic inflammation and improves endothelial function, but does not influence the increased carotid IMT in OSAHS patients.

Topics: Atherosclerosis; Body Mass Index; Carotid Artery Diseases; Continuous Positive Airway Pressure; Endothelin-1; Enzyme-Linked Immunosorbent Assay; Humans; Inflammation; Nitric Oxide; Polysomnography; Sleep Apnea, Obstructive; Tumor Necrosis Factor-alpha; Tunica Intima

Microparticles are deemed true biomarkers and vectors of biological information between cells. Depending on their origin, the composition of microparticles varies and the subsequent message transported by them, such as proteins, mRNA, or miRNA, can differ. In obstructive sleep apnea syndrome (OSAS), circulating microparticles are associated with endothelial dysfunction by reducing endothelial-derived nitric oxide production. Here, we have analyzed the potential role of circulating microparticles from OSAS patients on the regulation of angiogenesis and the involved pathway. VEGF content carried by circulating microparticles from OSAS patients was increased when compared with microparticles from non-OSAS patients. Circulating microparticles from OSAS patients induced an increase of angiogenesis that was abolished in the presence of the antagonist of endothelin-1 receptor type B. In addition, endothelin-1 secretion was increased in human endothelial cells treated by OSAS microparticles. We highlight that circulating microparticles from OSAS patients can modify the secretome of endothelial cells leading to angiogenesis.

Topics: Adult; Aged; Aorta; Apoptosis; Blotting, Western; Cell Adhesion; Cell-Derived Microparticles; Endothelial Cells; Endothelin B Receptor Antagonists; Endothelin-1; Flow Cytometry; Humans; Male; Middle Aged; Neovascularization, Physiologic; Oligopeptides; Piperidines; Receptor, Endothelin B; Sleep Apnea, Obstructive; Vascular Endothelial Growth Factor A; Young Adult

To explore the effects of allitridi capsules on endothelial function and clinical prognosis in coronary artery disease (CAD) patients with obstructive sleep apnea hypopnea syndrome (OSAHS).. A total of 80 CAD patients with OSAHS were randomly assigned to receive conventional treatment (control, n = 40) and additional allitridi treatment (120 mg/day, n = 40) for 6 months. Another 40 CAD patients without OSAHS and 30 healthy individuals were chosen as controls. Endothelial function was assessed by endothelium dependent flow-mediated dilation (FMD) with high-definition color Doppler ultrasound. Serum nitric oxide (NO) and plasma endothelin-1 (ET-1) levels were determined by enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay. The duration of follow-up was 1 year.. The baseline clinical characteristics were not different between control and allitridi groups (P > 0.05). Compared with CAD patients without OSAHS, FMD and serum NO level were significantly lower ((7.9 ± 1.5)% vs (11.2 ± 2.9)%, P = 0.011 and (71.11 ± 10.62) vs (86.28 ± 11.03) µmol/L, P = 0.007), plasma ET-1 level was markedly higher ((112.34 ± 17.22) vs (89.87 ± 11.56) ng/L, P = 0.025) in CAD patients with OSAHS. At Month 6 post-treatment, FMD and serum NO level were significantly higher ((12.1 ± 3.1)% vs (9.1 ± 1.6)%, P = 0.020 and (105.24 ± 17.01) vs (82.39 ± 11.12) µmol/L, P = 0.001) and plasma ET-1 level in the allitridi group was lower ((77.12 ± 9.65) vs (97.77 ± 11.04) ng/L, P = 0.001) than that in the control group. At Month 12 post-treatment, the incidence of MACE was lower in the allitridi group than that in the control group (8.3% vs 15.8%, P = 0.016).. Allitridi capsules significantly improved endothelial function in CAD patients with OSAHS.

Topics: Allyl Compounds; Capsules; Coronary Artery Disease; Endothelin-1; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Humans; Nitric Oxide; Prognosis; Sleep Apnea, Obstructive; Sulfides

Obstructive sleep apnoea (OSA) is a risk factor for cardiovascular disorders and in some cases is complication of pulmonary hypertension. We simulated OSA by exposing rats to cyclic intermittent hypoxia (CIH) to investigate its effect on pulmonary vascular endothelial dysfunction. Sprague-Dawley Rats were exposed to CIH (FiO2 9% for 1 min, repeated every 2 min for 8 h/day, 7 days/wk for 3 wk), and the pulmonary arteries of normoxia and CIH treated rats were analyzed for expression of endothelin-1 (ET-1) and ET receptors by histological, immunohistochemical, RT-PCR and Western Blot analyses, as well as for contractility in response to ET-1. In the pulmonary arteries, ET-1 expression was increased, and ET-1 more potently elicited constriction of the pulmonary artery in CIH rats than in normoxic rats. Exposure to CIH induced marked endothelial cell damage associated with a functional decrease of endothelium-dependent vasodilatation in the pulmonary artery. Compared with normoxic rats, ETA receptor expression was increased in smooth muscle cells of the CIH rats, while the expression of ETB receptors was decreased in endothelial cells. These results demonstrated endothelium-dependent vasodilation was impaired and the vasoconstrictor responsiveness increased by CIH. The increased responsiveness to ET-1 induced by intermittent hypoxia in pulmonary arteries of rats was due to increased expression of ETA receptors predominantly, meanwhile, decreased expression of ETB receptors in the endothelium may also participate in it.

Topics: Animals; Endothelin-1; Endothelium, Vascular; Gene Expression Regulation; Hypertension, Pulmonary; Hypoxia; Male; Pulmonary Artery; Rats; Rats, Sprague-Dawley; Receptors, Endothelin; Sleep Apnea, Obstructive; Vasoconstriction; Vasodilation

The role of oxidative stress in hypertensive elderly patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) is unknown.. The purpose was to evaluate the levels of big endothelin-1 (Big ET-1) and nitric oxide (NO) in elderly hypertensive patients with and without moderate to severe OSAHS.. Volunteers were hospitalized for 24 h. We obtained the following data: body mass index (BMI); 24-ambulatory blood pressure monitoring; and current medication. Arterial blood was collected at 7 pm and 7 am for determining plasma NO and Big ET-1 levels. Pulse oximetry was performed during sleep. Pearson's or Spearman's correlation and univariate analysis of variance were used for statistical analysis.. We studied 25 subjects with OSAHS (group 1) and 12 without OSAHS (group 2) aged 67.0 ± 6.5 years and 67.8 ± 6.8 years, respectively. No significant differences were observed between the groups in BMI; number of hours of sleep; 24-h systolic and diastolic BPs; awake BP, sleep BP and medications to control BP between groups. No differences were detected in plasma Big ET-1 and NO levels at 19:00 h, but plasma Big ET-1 levels at 7:00 h were higher in group 1 (p =0.03). In group 1, a negative correlation was also observed between the mean arterial oxyhemoglobin saturation level, 24-h systolic BP (p = 0.03, r = -0.44), and Big ET-1 (p = 0.04, r = -0.41).. On comparing elderly hypertensive patients with and without OSAHS having similar BP and BMI, we observed higher Big ET-1 levels After sleep in the OSAHS group. NO levels did not differ between the hypertensive patients with or without OSAHS.

Topics: Aged; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Body Mass Index; Endothelin-1; Female; Humans; Hypertension; Male; Nitric Oxide; Oxidative Stress; Oximetry; Reference Values; Sleep Apnea, Obstructive; Statistics, Nonparametric; Time Factors

To explore the treatment effect of H-UPPP on patients with obstructive sleep apnea hypopnea syndrome (OSAHS).. Seventy-nine patients were enrolled in our study. Among which 49 patients were done with H-UPPP, and the other 30 patients were done with UPPP. AHI and LSaO2 were monitored by polysomnography and plasma endothelins-1 were tested with enzyme linked immunosorbent assay (ELISA) before and after operation.. Forty-one patients were improved with reduced snoring and daytime sleepiness one year after operation in H-UPPP group,and the overall efficiency was 83.7%. Twenty-six patients were improved with reduced snoring and daytime sleepiness one year after operation in UPPP group, and the overall efficiency was 86.7%. There were significant differences of AHI, LSaO2 and ET-1 before and after operation between the two groups. Negative correlation was showed between AHI and LSaO2, also between LSaO2 and ET-1.. Both H-UPPP and UPPP were proved to be effective to patients with OSAHS. The perioperative complications with H-UPPP was less than UPPP.

Topics: Adult; Apnea; Disorders of Excessive Somnolence; Endothelin-1; Female; Humans; Male; Middle Aged; Palate, Soft; Pharynx; Polysomnography; Sleep Apnea, Obstructive; Sleep Stages; Snoring; Uvula

Obstructive sleep apnea (OSA) causes endothelial dysfunction and is an independent risk factor for hypertension and cardiovascular diseases. Although vasoactive agents and sympathoexcitation have been implicated and operational in the pathogenesis of hypertension associated with OSA the exact mechanisms underlying hypertension have not been established. Soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) are released under hypoxic stress and cause endothelial dysfunction and hypertension in humans and animals. The present study was conducted to investigate the role of these antiangiogenic proteins in OSA and to determine their clinical significance.. In 22 untreated OSA patients with apnea-hypopnea index ≥30 events/h (11 with hypertension and 11 without hypertension) we measured plasma concentrations of endothelin-1, epinephrine, norepinephrine, nitric oxide metabolites, sFlt-1 and sEng.. The apnea-hypopnea indices were 81±11 and 76±9 events/h (P=ns) and the sleep times with SaO(2)<90% were 42±13 and 39±13 min (P=ns) for normotensives and hypertensives, respectively. Both groups had similarly elevated levels of catecholamines with normal endothelin-1 levels. Nitric oxide metabolites were depressed in both groups with no inter-group differences. On the other hand, both sFlt-1 (90.0±4.6 pg/ml vs. 74.0±4.4 pg/ml, P=0. 018) and sEng (4.9±0.34 ng/ml vs. 3.50±0.42 ng/ml, P=0.016) were significantly elevated in the hypertensive patients compared to the normotensive subjects.. These data show that sFlt-1 and sEng are increased in the circulation of patients with OSA and hypertension and suggest that they may be involved in the pathogenesis of hypertension.

Topics: Antigens, CD; Cardiovascular Diseases; Endoglin; Endothelin-1; Endothelium, Vascular; Epinephrine; Female; Humans; Hypertension; Male; Middle Aged; Nitric Oxide; Norepinephrine; Polysomnography; Receptors, Cell Surface; Risk Factors; Sleep Apnea, Obstructive; Vascular Endothelial Growth Factor Receptor-1

This study, in optimally treated CAD patients with newly diagnosed OSA, focused on (1) The relationships between OSA and serum biomarkers of four potential pathways of cardiovascular injury in OSA: high-sensitivity C-reactive protein (hs-CRP), endothelin-1 (ET-1), N terminal pro B type natriuretic peptide (NT-proBNP) and fibrinogen; and (2) The effect of continuous positive airway pressure (CPAP) therapy on these markers. 151 Chinese patients with proven CAD and standard medication were enrolled. After polysomnography, patients were classified into four groups according to apnea-hypopnea index (AHI): no OSA (n = 25); mild OSA (n = 50); moderate OSA (n = 43); severe OSA (n = 33). Morning levels of hs-CRP, ET-1, NT-proBNP and fibrinogen were assayed and repeated in severe OSA patients after 3-months CPAP treatment. Hs-CRP was greater in patients with severe OSA than those with no OSA or mild OSA (P = 0.001, P = 0.003; respectively). After adjustment for confounders, the hs-CRP levels correlated most strongly with AHI and oxygen desturation index (ODI) (r = 0.439, P < 0.001; r = 0.445, P < 0.001; respectively). In stepwise multiple linear regressions, the strongest predictor of hs-CRP levels was ODI (P < 0.001). After 3 months of CPAP treatment, the hs-CRP levels deceased (P = 0.005) in CAD patients with severe OSA. In CAD patients on current optimal medications, hs-CRP is significantly correlated with the severity of OSA, and the elevated hs-CRP levels can be decreased by CPAP. This suggests that OSA could activate vascular inflammation in CAD patients despite current best practice medications.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Continuous Positive Airway Pressure; Cross-Sectional Studies; Endothelin-1; Female; Fibrinogen; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Polysomnography; Sleep Apnea, Obstructive

The endothelin (ET)-system is composed of three endothelins, two receptors and two enzymes. The study of this system presents a great interest to understand the cardiovascular physiopathology. The ET-system is involved in cardiac organogenesis, angiogenesis and vascular tone homeostasis. Its role in arterial pulmonary hypertension, arterial hypertension and atherosclerosis has been shown. The numerous ET-system's targets suggest that it could be involved in pathologies which bring together various cardiovascular disorders such as the obstructive sleep apnoea syndrome. Thus, the ET-system generates today a lively interest for experimental and clinical trials.

Topics: Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Clinical Trials as Topic; Endothelin-1; Endothelins; Humans; Organogenesis; Sleep Apnea, Obstructive

Topics: Endothelin-1; Humans; Risk Factors; Sleep Apnea, Obstructive

Obstructive sleep apnea (OSA) is a recognized risk factor for cardiovascular disorders. Thus, an association between endothelin-1 (EDN1) and OSA can be assumed. We investigated a cohort of 364 consecutive patients (age 57 +/- 10 years) with mild to severe OSA for the EDN1 variant Lys198Asn (G/T) and endothelin plasma levels and compared them with 57 controls. The Lys198Asn genotype was significantly associated with the apnea/hypopnea index (AHI) with a median of 30/h of sleep for GG, 27/h for GT and 59/h for TT genotype (p < 0.05). Further stratification of patients into 2 groups by body mass index (BMI) revealed a strong association between AHI and Lys198Asn polymorphism in 191 obese patients (p = 0.005), whereas in 173 nonobese patients, we observed no association. A substantial effect by BMI on OSA severity was seen with multiple linear regression (p < 0.001). However, this effect was modified by the Lys198Asn polymorphism and by gender: the AHI increase per unit of BMI was more pronounced in males than in females, and about 1.3 times greater in homozygous carriers of the mutant allele than in other carrier groups. EDN1 plasma levels of untreated OSA patients and of patients treated with nasal continuous positive airway pressure were not elevated compared with controls. Our results indicate that the Lys198Asn polymorphism is associated with the severity of OSA in obese subjects. The EDN1 plasma level cannot be used as a marker for OSA or its severity.

Topics: Aged; Endothelin-1; Female; Gene Frequency; Genotype; Humans; Male; Middle Aged; Obesity; Point Mutation; Risk Factors; Severity of Illness Index; Sleep Apnea, Obstructive

Cardiovascular (CV) diseases are a leading cause of mortality and they are frequent in patients with the obstructive sleep apnea syndrome (OSAS).. In this study we investigated if OSAS influences CV function independently of other CV risk factors frequently present in these patients (e.g. obesity, high blood pressure).. We compared plasma markers of endothelial dysfunction, asymmetric dimethylarginine (ADMA) and endothelin-1 (ET-1), and atherosclerosis progression (soluble fraction of the CD40 ligand, sCD40L) in OSAS patients with (n = 23) and without (n = 18) concurrent CV risk factors, as well as in healthy subjects (n = 23).. Plasma ADMA (p < 0.01) and sCD40L (p < 0.05) were abnormally increased in patients with OSAS versus healthy controls, but they were not influenced by the presence or absence of CV risk factors in OSAS. ET-1 levels were not different between the three groups of subjects studied.. OSAS is associated with endothelial injury and atherosclerosis progression independently of other CV risk factors.

Topics: Adult; Arginine; Atherosclerosis; Cardiovascular Diseases; Case-Control Studies; CD40 Ligand; Endothelin-1; Humans; Male; Middle Aged; Risk Factors; Sleep Apnea, Obstructive

Our aim was to investigate the involvement of the endothelin (ET) system in the cardiovascular consequences of intermittent hypoxia (IH).. Obstructive sleep apnea (OSA) syndrome is an important risk factor for cardiovascular morbidity. Chronic IH, a major component of OSA, is thought to be responsible for most of the cardiovascular complications occurring during OSA, but the underlying mechanisms remain to be determined.. Chronic IH was applied in rats genetically prone to develop hypertension (spontaneous hypertensive rats [SHR]) and their normotensive controls. The cardiovascular effects were assessed in vivo and in Langendorff perfused hearts. Hypoxia inducible factor (HIF)-1 activity and targeting of the myocardial ET-1 gene and activation of the ET system were investigated using tissue chromatin immunoprecipitation, enzyme-linked immunoadsorbent assay, immunostaining, and Western blotting.. Chronic IH enhanced hypertension development and infarct size in SHR compared with that seen in control rats. This was accompanied by an increase in myocardial big ET-1, ET-1, and ET-A receptor expression and by an enhanced coronary vascular reactivity to ET-1 in SHR only. Myocardial HIF-1 activity was increased, and HIF-1 was shown to be linked to the promoter of the myocardial ET-1 gene after chronic IH only. Moreover, administration of bosentan, a mixed ET receptor antagonist, during chronic IH prevented both the increase in blood pressure and in infarct size.. In SHR, activation of the ET system, mediated by HIF-1 activity, is responsible for the enhanced susceptibility to chronic IH and for its associated cardiovascular consequences leading to hypertension and ischemic injury. Furthermore, the beneficial effects of bosentan suggest exploring ET antagonists as possible therapeutic tools in OSA.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Bosentan; Disease Models, Animal; Endothelin-1; Genetic Predisposition to Disease; Heart; Hypertension; Hypoxia; Hypoxia-Inducible Factor 1; Male; Myocardial Infarction; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Sleep Apnea, Obstructive; Sulfonamides

Topics: Animals; Cardiovascular Diseases; Endothelin-1; Humans; Rats; Sleep Apnea, Obstructive

Topics: Animals; Carotid Body; Cats; Endothelin-1; Hypoxia; Male; Oxygen; Oxygen Consumption; Receptor, Endothelin A; Receptor, Endothelin B; Sleep Apnea, Obstructive

The mechanisms involved in development and maintenance of hypertension in obstructive sleep apnea (OSA) are not clarified. We hypothesize that patients with OSA have an abnormal nocturnal level of some vasoactive hormones during the night.. We studied 32 patients with OSA and 19 healthy control subjects during The night-time with serial determinations of endothelin-1 (ENDO-1), angiotensin II (Ang II), renin (PRC), aldosterone (ALDO) in plasma, and blood pressure (BP), and oxygen saturation.. Patients with OSA had a higher plasma level of ENDO than healthy controls and the mean nocturnal level of ENDO correlated significantly to the apnea-hypopnea index (AHI) as a measure of the severity of OSA. This correlation remained statistically significant after analysis in a general linear model with correction for confounders. Patients with OSA also had a significantly higher BP than healthy controls and the ambulatory BP correlated positively to the AHI in patients with OSA. No significant differences were measured in Ang II, PRC, and ALDO between the two groups. The correlation between AHI and ENDO supports OSA as a stimulus of endothelin release or increased endothelin levels contributing to the severity of OSA.. Endothelin seems to be a pathogenic factor in generating hypertension in OSA.

Topics: Adult; Aldosterone; Angiotensin II; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Case-Control Studies; Endothelin-1; Female; Heart Rate; Humans; Hypertension; Male; Middle Aged; Oxygen; Renin; Sleep Apnea, Obstructive

To explore the role of sympathetic nerve activity and vessel endothelial function in the pathogenesis of hypertension in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS).. Based on polysomnography (PSG), blood pressure (BP) and disease history, 93 subjects were divided into four groups: OSAHS with hypertension (OH), OSAHS without hypertension (O), hypertension without OSAHS (H), normal control (N). In addition to the blood pressure measurement, blood samples were collected before and after sleep during the PSG testing night to measure norepinephrine, endothelin, and NO levels. Urine samples were also collected during this time to test the level of vanillyl mandalic acid (VMA).. Patients in OH group and O group had significantly increased plasma NE value (P < 0.05) in the next morning compared with those before sleep and the change was more significant in OH group compared to O group (P < 0.01). Pre-and after-sleep urine VMA levels in all groups showed no significant differences. Plasma NE and ET levels in OSAHS with and without hypertension after sleep were positively correlated with mean arterial pressure (MAP), apnea-hypopnea index (AHI), number of oxygen desaturation >or= 4% per hour (ODI(4)), percentage of time of oxygen saturation lower than 90% (T90) and correlated negatively with minimum arterial oxygen saturation (minSaO(2)) and mean arterial oxygen saturation (MSaO(2)). Moreover, plasma ET also correlated positively with MAP, AHI, maximum apnea time, total apnea time. Compared with other groups plasma ET value increased significantly and serum NO value decreased in the next morning in both O and OH group. Serum NO value after one night sleep in both hypertensive and norhypertensive OSAHS patients was negatively correlated with MAP, AHI, maximum apnea time, total apnea time, ODI(4), T90, and positively with minSaO(2) and MSaO(2).. Sympathetic nerve activation and endothelial dysfuntion characterized by an imbalance of endothelium-derived systolic and diastolic factors may play an important role in the development of transient and sustained increase of blood pressure in patients with OSAHS.

Topics: Adult; Endothelin-1; Endothelium, Vascular; Female; Humans; Hypertension; Male; Middle Aged; Nitric Oxide; Norepinephrine; Polysomnography; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Sympathetic Nervous System

To investigate the effects of intermittent hypoxia (IH) on the expression of endothelin-1 (ET-1), nitric oxide (NO), and nitric oxide synthase (NOS) in endothelium, and to evaluate the role of functional disorder of endothelium in the mechanism of obstructive sleep apnea syndrome (OSAS) induced hypertension.. Human umbilical vein endothelial cells (HUVECs) of the line ECV304 were cultured and divided into 4 groups: IH group (exposed to 1.5% O(2) for 15 s and 21% O(2) for 1 min 15 s, 3 min 45 s, 5 min 15 s, or 8 min 15 s respectively alternatively with 60 episodes), intermittent normal oxygen group (exposed to 21% O(2) for 15 s and 225 s alternatively with 60 episodes), continuous hypoxia group (exposed to 1.5% for 15 min), and blank control group. Then the culture fluid was collected. The levels of activity of ET-1 (EIA) NO, and NOS were detected by enzyme immune assay, nitric acid reductase method, and chemical colorimetric analysis respectively. RT-PCR was used to detect the mRNA expression of endothelial NOS (eNOS).. Compared with those of the intermittent normal oxygen group and blank control groups the ET-1 levels of the 4 IH sub groups were significantly higher (F = 28.453, P = 0.000), the NO levels ere significantly lower F = 65.252, P = 0.000), the NOS activity levels were significantly lower (F = 5.969, P = 0.008), and eNOS mRNA was significantly down-regulated (F = 16.630, P = 0.000). Compared with continuous hypoxia group with the exposure time equivalent to the accumulated hypoxia time (15 s with 60 episodes) of the IH group, the ET-1 level was significantly higher (t = 2.742, P = 0.024), the NO level was significantly lower (t = 3.347, P = 0.004), the NOS activity level was significantly lower (t = 3.989, P = 0.004), and the eNOS mRNA expression was down-regulated (t = 5.045, P = 0.000). In the different IH group along with the prolongation of the re-oxygenation time from 105 s to 495 s, while maintaining the duration of hypoxic episodes at 15 s, the ET-1 level increased (F = 213.254, P = 0.000), the NO level decreased (F = 15.747, P = 0.000), NOS activity level decreased (F = 2.933, P = 0.048), and eNOS mRNA expression was down-regulated (F = 5.954, P = 0.002). However, there was a tendency for ET-1 to decrease and the NO system indicators when the re-oxygenation time was 8 min 15 s.. Hypoxia and re-oxygenation both cause endothelium dysfunction and unbalance of NO/ET-1, which is important to OSAS with hypertension.

Topics: Analysis of Variance; Cell Hypoxia; Cell Line; Endothelial Cells; Endothelin-1; Humans; Immunoassay; Nitric Oxide; Nitric Oxide Synthase Type III; Oxygen; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sleep Apnea, Obstructive; Umbilical Veins

To explore the mechanism of the effect of chronic intermittent hypoxia (CIH), an important pathophysiological state of sleep apnea syndrome (SAS), on cardiovascular system.. Thirty male ICR mice were divided into three groups: an experimental group, an air mimic control group and a blank control group. Immunohistochemistry was used to examine the expression of hypoxia inducible factor-1alpha (HIF-1alpha) and inducible nitric oxide synthase (NOS-2) in the myocardial cells. Enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma concentration of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1).. The expression of HIF-1alpha in myocardial cells of the experimental group significantly increased compared with that of the air mimic control group (t = 3.54, P < 0.05), and that of the blank control group (t = 2.92, P < 0.05). The expression of HIF-1alpha in myocardial cells of the air mimic control group was not significantly different from that of the blank control group (P > 0.05). The plasma concentration of VEGF of the experimental group [(9.57 +/- 1.41) ng/ml] was significantly higher than that of the blank control group [(8.10 +/- 0.62) ng/ml, q = 4.27, P < 0.05], and that of the air mimic control group [(8.32 +/- 0.99) ng/ml, q = 3.64, P < 0.05]. While the plasma concentration of ET-1 of the experimental group [(3.31 +/- 0.81) ng/ml] was significantly higher than that of the blank control group [(2.50 +/- 0.72) ng/ml, q = 3.64, P < 0.05], it was not significantly different from that of the air mimic control group [(2.69 +/- 0.43) ng/ml, P > 0.05]. There was no significant difference between the expression of NOS-2 in myocardial cells of all groups (P > 0.05).. CIH enhances the expression of HIF-1alpha and its target gene products VEGF and ET-1, and therefore affects the cardiovascular system.

Topics: Animals; Endothelin-1; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Male; Mice; Mice, Inbred ICR; Nitric Oxide Synthase Type II; Sleep Apnea, Obstructive; Transcription Factors; Vascular Endothelial Growth Factors

Assessment of plasma endothelin-1 (ET-1) reveals conflicting results in cerebral and noncerebral conditions. Obstructive sleep apnea (OSA) syndrome has been used as a definite challenge for the investigation of endothelin measurements. Despite marked sleep-related breathing disturbances in untreated patients peripherally measurable ET-1 concentrations remained within the normal range and did not change after an appropriate therapy with continuous positive airway pressure (CPAP). In contrast, its precursor, big ET-1, was considerably elevated in untreated patients and dropped to normal values after long-term CPAP depending on compliance. Relatively stable big ET-1 elevations in untreated patients, during sleep and wakefulness, suggest that a general endothelial alteration beyond that explained by a direct impact of nocturnal breathing disturbances on the vascular system occurs. CPAP-therapy effectively lowered plasma big ET-1 in compliant patients and thus possibly their related risk for vascular diseases. Big ET-1 has been demonstrated to be a more appropriate marker of endothelial alteration than ET-1 because of its longer half-life. Simultaneous measurements are to be recommended.

Topics: Adult; Aged; Arteries; Continuous Positive Airway Pressure; Endothelin-1; Female; Humans; Male; Middle Aged; Oxygen; Patient Compliance; Protein Precursors; Sleep Apnea, Obstructive; Time

To observe the changes of thromboxane B2 (TXB2), rennin, angiotensin II (AT-II), endothelin 1 (ET-1) and anticardiolipin antibody (ACA) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) before and after the operation.. Fifty-four cases of OSAHS confirmed by polysomnography (PSG) were selected as the OSAHS group and 20 normal donors without OSAHS were selected as the control group. Plasma levels of TXB2, rennin, AT- II, ET-1 and ACA were detected by enzyme-linked immunosorbent assay (ELISA).. Plasma levels of TXB2, rennin, AT-II, ET-1 and ACA were higher in patients with OSAHS than those in control group (P < 0.05 or P < 0.01), and the operation therapy decreased them significantly (P < 0.05 or P <0.01). All the plasma parameters were correlated positively with AHI, and negatively with SaO2.. The results indicate the patients with OSAHS were susceptible to thromboembolism disease. Operation therapy is effective in correcting TXB2, rennin, AT-II, ET-1 and ACA.

Topics: Angiotensin II; Antibodies, Antiphospholipid; Case-Control Studies; Chymosin; Endothelin-1; Humans; Sleep Apnea, Obstructive; Thromboxane B2

Topics: Adult; Arrhythmias, Cardiac; Cardiovascular Diseases; Child; Comorbidity; Coronary Artery Disease; Endothelin-1; Endothelium, Vascular; Epidemiologic Studies; Genetic Predisposition to Disease; Heart Failure; Humans; Hypertension; Male; Obesity; Risk Factors; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Thrombophilia

To explore the role of endothelin-1 (ET-1) in the pathogenesis of hypertension in obstructive sleep apnea hypopnea syndrome (OSAHS).. The levels of serum ET-1 in 30 OSAHS patients accompanied by hypertension, 30 normotensive OSAHS patients and 30 healthy controls were measured by ET-1 enzyme immunoassay kit. Meanwhile the correlation about the concentration of ET-1 in OSAHS patients with the clinic, polysomnography (PSG) parameters was analyzed.. OSAHS patients with or without hypertension compared with snoring group and normal people, the sleep structure was significantly disturbed. The time percentages of awake and stage I sleep were increased, while stage II sleep decreased significantly in OSAHS patients than those in snoring group (P < 0.01, respectively). There were no significantly difference about the sleep structure in the two OSAHS groups. The levels of serum ET-1 (mean +/- s) were significantly higher in OSAHS patients accompanied by hypertension and normotensive OSAHS patients(42.5 +/- 8.4) ng/L and (38.6 +/- 4.7) ng/L respectively than those in the healthy controls(33.1 +/- 5.4) ng/L (P < 0.01, respectively). In the two OSAHS groups, the levels of serum ET-1 were significantly higher in OSAHS patients accompanied by hypertension than those in the normotensive OSAHS patients (P < 0.05). There were positive correlations between the concentration of ET-1 and the apnea hypopnea index (AHI) in all the 60 OSAHS patients with and without hypertension (r = 0.334, P < 0.01). There were negative correlations between the concentration of ET-1 and the lowest oxygen desaturation in all the 60 OSAHS patients with and without hypertension (r = -0.230, P < 0.05).. These results indicate that the sleep disordered breathing and hypoxia may contribute to the elevation of ET-1 in the OSAHS patients and OSAHS patients accompanied by hypertension. ET-1 may play an important role in the pathogenesis of OSAHS-induced hypertension.

Topics: Adult; Endothelin-1; Female; Humans; Hypertension; Male; Middle Aged; Polysomnography; Sleep; Sleep Apnea, Obstructive

To investigate the influence of nasal continual positive airway pressure (nCPAP) on the plasma levels of thromboxane B(2) (TXB(2)), renin, angiotensin II (AT-II), endothelin 1 (ET-1), cyclic AMP (cAMP) and cyclic GMP (cGMP) and evaluate their clinical significance.. 20 patients with OSAS without cardiovascular complications and 20 nromal controls were enrolled in the study, who were monitored with PSG, and then treated with nCPAP during the second night. All the plasma parameters were measured after PSG monitoring and nCPAP management with radio-immunoassay.. Before nCPAP, plasma levels of TXB(2), renin, and AT-II were higher in patients with OSAS than those in control (P < 0.05); Meanwhile, the plasma levels of ET-1, cAMP, and cAMP/cGMP were significantly higher in patients group than those in control (P < 0.01).. Patients with severe OSAS may have disturbances in neuro-regulation and changes in plasma level of TXB(2), renin, AT-II and ET-1, which indicates that the vasoactive substance might be related to the hypoxemia and disturbance in neuro-regulations, and might play an important role in the development of hypertension and other cardiovascular disorders. nCPAP therapy can correct the abnormalities of some vasoactive substances.

Topics: Angiotensin II; Cyclic AMP; Cyclic GMP; Endothelin-1; Positive-Pressure Respiration; Renin; Sleep Apnea, Obstructive; Thromboxane B2

Topics: Endothelin-1; Humans; Sleep Apnea, Obstructive