Plasma Endothelin-1 Levels Research Articles

Elevations of local intravascular pressures release vasoactive substances in humans

The wall stiffness of arteries and arterioles adapts to the long-term demands imposed by local intravascular pressure. We investigated whether substances capable of inducing acute and long-term effects on arterial wall stiffness are released locally into the bloodstream in response to an acute marked increase in local intravascular pressure in the blood vessels of the human arm. Experiments were performed on ten subjects positioned in a pressure chamber with one arm extended through a hole in the chamber door and kept at normal atmospheric pressure. Intravascular pressure was increased in the arm, by a stepwise increase in chamber pressure up to +150 mmHg. Diameter and flow were measured in the brachial artery by Doppler ultrasonography. Blood samples were drawn simultaneously from both arms before, during, immediately after and 2 h after the release of the chamber pressure. Plasma levels of endothelin-1 (ET-1), vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2) and angiotensin II (Ang-II) were measured. Elevation of chamber pressure by 150 mmHg increased local arterial distending pressure to about 220-260 mmHg, resulting in an increase in brachial artery diameter of 9% and flow of 246%. The pressure stimulus increased the plasma levels of ET-1 and Ang-II, but not of VEGF-A or FGF-2 in the test arm. The local release of the vasoconstrictors ET-1 and Ang-II in response to markedly increased distending pressure may reflect one mechanism behind adaptation to acute and long-term changes in intravascular pressure.

Effect of the flavonoid fraction of Lithocarpus polystachyus Rehd. on spontaneously hypertensive and normotensive rats

Ethnopharmacological relevanceLilhocarpus polystachys Rehd. (Sweet Tea, ST) is a folk herbal medicine that has been traditionally used as a natural remedy for hypertension in China, whose mechanism remains unveiled. Flavonoid fraction is considered as the major active components in ST. This study aimed to provide experimental evidence for the anti-hypertension activity of flavonoid fraction of ST (ST-F) and investigate the underlying mechanism. The effect of ST-F on the blood pressure of normotensive rats was also to be determined. Materials and methodsSpontaneously hypertensive rats (SHRs) were treated with ST-F daily for 10 weeks. Blood pressure of SHRs was measured before and biweekly during ST-F treatment. Subsequently, animals were sacrificed either immediately at the end of treatment or 2 weeks after ST-F treatment discontinuance. The activities of plasma rennin (PRA), angiotensin II (Ang-I), endothelin (ET), nitric oxide (NO), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured as well as skin microcirculatory flux. In normotensive rats, blood pressure was determined after six months' treatment of ST-F. ResultsST-F treatment significantly reduced the blood pressure of SHRs along with decreasing plasma levels of PRA and Ang II. ST-F did not show obvious effects on plasma levels of ET, NO or SOD, but it significantly decreased the plasma level of MDA and improved skin microcirculatory flux. Compared to the anti-hypertensive drug enalapril, ST-F showed a modest effect on lowering blood pressure of SHRs without obvious withdrawal reactions. But long-term intake of ST-F did not change the blood pressure in normotensive rats. ConclusionST-F had an antihypertensive effect on SHRs. The underlying mechanism could be related to modulation on the rennin–angiotensin–aldosterone system (RAAS) and antioxidation system, as well as regulation of skin microcirculation. Compared to its anti-hypertensive effect on SHRs, ST-F did not cause hypotension in normotensive rats. The results indicated that ST-F could potentially be used as natural drugs or functional foods for preventing hypertension.

Regorafenib induces rapid and reversible changes in plasma nitric oxide and endothelin-1.

Hypertension is a toxicity of antiangiogenic therapies and a possible biomarker that identifies patients with superior cancer outcomes. Understanding its mechanism will aid in treatment and could lead to the development of other biomarkers for predicting toxicity and anticancer efficacy. Recent evidence implicates nitric oxide (NO) suppression and endothelin-1 (ET-1) stimulation as potential mechanisms leading to antiangiogenic therapy-induced hypertension. The aim of this study was to evaluate the effects of regorafenib, a novel broad-spectrum kinase inhibitor with activity against multiple targets, including vascular endothelial growth factor receptor 2 inhibition, on NO and ET-1 levels. Regorafenib was administered to 32 subjects with gastrointestinal stromal tumor on a 3-week-on, 1-week-off basis. Plasma levels of NO and ET-1 were measured at baseline, 2, 4, and 6 weeks of therapy. Data analysis was by Wilcoxon rank-sum and paired t-tests. Twenty subjects (63%) developed regorafenib-induced hypertension. Two weeks after starting regorafenib therapy, plasma ET-1 levels increased (25% increase, P < 0.05) and NO was suppressed (20% decrease, P < 0.05). These normalized after 1-week washout but ET-1 rose again by 30% (P < 0.05) and NO fell by 50% (P < 0.05) after restarting regorafenib. These findings indicate that regorafenib induces a coordinated and reversible suppression of NO and stimulation of ET-1. Whether NO and ET-1 might predict therapeutic efficacy in these patients requires further study.

Protective effects of endothelin-1 receptor antagonist (BQ-123) against lung ischemia-reperfusion injury on the model of acute pulmonary embolism in rabbits

Objective To explore the protective effects of endothelin-1 ( ET-1 ) receptor antagonist BQ-123 against ischemia-reperfusion injury after thrombolysis in acute pulmonary embolism.Methods Twenty-four big-ear Japanese rabbits (no limit of male or female) were divided into 4 groups randomly ( n =6 in each group):sham group ( sham-operated group),PE group ( pulmonary embolism group),UK group (thrombolysis group),BQ group ( UK + BQ-123 group).We detected the levels of ET-1 in the venous blood plasma and mean pulmonary arterial pressure (MPAP) before and 0.5,2,4 h after embolization.The ratio of lung tissue wet/dry (W/D),the superoxide dismutase (SOD) activity and malondialdehyde (MDA) content at the end of the experiment were measured.Results As compared with sham group [(18.92 ±0.63) mm Hg(1 mm Hg=0.133 kPa) ],the MPAP in PE group (19.01 ±0.60) mm Hg,UK group (20.14 ±0.85) mm Hg,and BQ group ( 19.79 ±0.78) mm Hg was increased significantly at 0.5 h after embolization (P ＜0.05).There was no significant difference in MPAP between BQ group and UK group at 2 h and 4 h after embolization.The levels of plasma ET-1 in BQ group were reduced more significantly than UK group at 4 h after embolization.As compared with sham group,the W/D and MDA content were increased,but SOD activity was reduced in PE group and UK group at the end of the experiment,and the same results were obtained between UK group and PE group (P ＜ 0.05).The W/D ratio and MDA content were lower,and SOD activity was higher in BQ group than in UK group (P ＜0.05).Conclusion Lung ischemia-repeffusion injury appeared in thrombolysis after acute pulmonary embolism,and BQ-123 may exert the antagonistic effets. Key words: Acute pulmonary embolism; Lung ischemia; Reperfusion injury; Endothelia; Endothelia receptor antagonist

Effects of Shenmai injection on the expression of endothelin in patients with severe acute pancreatitis

Objective To explore the changes of plasma endothelin(ET) as well as the effects of Shenmai in patients with severe acute pancreatitis (SAP).Methods Sixty patients with SAP were collected,and divided into routine treatment group (group A) and Shenmai treatment group (group B).The clinical data and ET levels were analyzed.Results The levels of ET were significantly higher in group A than those in group B at the day 2 and 4 [ ( 80.36 ± 11.05 ) vs (98.18 ± 11.83 ),and (93.63 ± 8.59) vs ( 107.53 ± 9.26) ] ( both P ＜ 0.05 ).The levels of ET were significantly higher in group A than those in group B at the day 7 (76.25 ± 10.81 vs 93.17 ± 12.42,P ＜0.01 ).There was no significant difference between group A and group B in age,gender,andAPACHE Ⅱ score(all P＞0.05).Conclusion Shenmai injection can effectively reduce the plasma levels of ET in SAP patients,and exert its therapeutic effect through improving microcirculation of SAP patients. Key words: Severe acute pancreatitis; Endothelin; Shenmai injection

Cardiac overexpression of metallothionein rescues cold exposure-induced myocardial contractile dysfunction through attenuation of cardiac fibrosis despite cardiomyocyte mechanical anomalies

Cold exposure is associated with an increased prevalence of cardiovascular disease although the mechanism is unknown. Metallothionein, a heavy-metal-scavenging antioxidant, protects against cardiac anomalies. This study was designed to examine the impact of metallothionein on cold exposure-induced myocardial dysfunction, intracellular Ca2+ derangement, fibrosis, endoplasmic reticulum (ER) stress, and apoptosis. Echocardiography, cardiomyocyte function, and Masson trichrome staining were evaluated in Friend virus B (FVB) and cardiac-specific metallothionein transgenic mice after cold exposure (3 months, 4°C). Cold exposure increased plasma levels of norepinephrine, endothelin-1, and TGF-β; reduced plasma NO levels and cardiac antioxidant capacity; enlarged ventricular end-systolic diameter; compromised fractional shortening; promoted reactive oxygen species (ROS) production and apoptosis; and suppressed the ER stress markers Bip, calregulin, and phospho-eIF2α, accompanied by cardiac fibrosis and elevated levels of matrix metalloproteinases and Smad-2/3 in FVB mice. Cold exposure-induced echocardiographic, histological, ER stress, ROS, apoptotic, and fibrotic signaling changes (but not plasma markers) were greatly improved by metallothionein. In vitro metallothionein induction by zinc chloride ablated H2O2- but not TGF-β-induced cell proliferation in fibroblasts. In summary, our data suggest that metallothionein protects against cold exposure-induced cardiac anomalies possibly through attenuation of myocardial fibrosis.

Effect of Nisoldipine and Olmesartan on Endothelium‐Dependent Vasodilation in Essential Hypertensive Patients

To investigate whether nisoldipine and olmesartan improve endothelial function, decrease asymmetric dimethylarginine (ADMA) and alleviate the inflammatory and oxidative process. Fifty-five essential hypertensive patients were randomized to receive nisoldipine or olmesartan for 8 weeks according to a parallel-group, active-controlled, single blind study, and 28 matched normotensive subjects served as healthy controls. Flow-mediated dilation (FMD), and plasma levels of nitric oxide (NO), endothelin-1 (ET-1), high-sensitive C-reactive protein (hs-CRP), 8-isoprostane (also named 8-isoPGF2α), and ADMA were determined. At baseline, the plasma levels of ADMA, ET-1, hs-CRP, and 8-isoPGF2α were markedly higher in patients with essential hypertension than in normotensive subjects (P < 0.05). A significant positive correlation was observed between plasma levels of ET-1 and ADMA in patients with essential hypertension, but not in normotensive subjects. The NO plasma concentrations were significantly lower in patients with essential hypertension than in normotensive subjects. Furthermore, hypertensive subjects demonstrated significantly lower FMD than healthy control (P < 0.05). Nisoldipine and olmesartan significantly and similarly reduced blood pressure in patients with essential hypertension (P < 0.001). At the end of the 8-week treatment, plasma ADMA and ET-1 levels were decreased significantly (P < 0.01). FMD increased significantly in nisoldipine or olmesartan-treated patients (P < 0.05). A significant decrease in plasma hs-CRP contents was observed in patients receiving nisoldipine (P < 0.05). The findings demonstrate that nisoldipine and olmesartan both improve FMD in patients with essential hypertension. This may be associated with decreased circulating levels of CRP, ET-1, and ADMA.

Blunted exercise‐induced vasodilation in familial hypercholesterolemic swine does not involve enhanced ET‐1‐mediated vasoconstriction

Hypercholesterolemia causes endothelial dysfunction and activation of the vascular endothelin‐1 (ET‐1) system. The procontractile effect of ET‐1 action on resistance vessels would therefore be expected to limit exercise‐induced vasodilation. To assess the role of hypercholesterolemia on ET‐1 activation and exercise‐induced vasodilation, we compared the effects of ET receptor blockade in instrumented Yucatan (Y) and familial hypercholesterolemic (FH) swine, at rest and during exercise. Exercise induced systemic vasodilation, measured as systemic vascular conductance index (SVCi = SVC/kg bodyweight), that was reduced in FH swine (36%) compared to Y swine (91%). Unexpectedly, the ETA/ETB receptor blocker tezosentan did not enhance exercise‐induced vasodilation in FH swine and the vasodilator effect of tezosentan at rest was reduced in FH swine (16%) versus Y swine (48%). Isolated skeletal muscle 2A arterioles from FH swine demonstrated enhanced sensitivity to ET‐1; however, plasma ET‐1 levels tended to be lower in conscious FH swine compared to Y swine (p=0.08). Thus, our data suggest that although the skeletal muscle vasculature of FH swine exhibits enhanced sensitivity to ET‐1, an ET‐1‐mediated enhancement of systemic vascular tone does not account for the reduced exercise‐induced dilation in FH swine, possibly as a result of reduced production/release of ET‐1 in FH swine. Supported by NIH‐HL52490.

Circulating levels of endothelin-1 (ET-1) and its precursor (Big ET-1) in breast cancer early diagnosis

Deregulation of the endothelin system, comprised of endothelin-1 (ET-1), its isoforms (ET-2 and ET-3) and their receptors (ET(A)R and ET(B)R), is under investigation in various types of human cancer. ET-1 has been suggested to participate in breast cancer development and progression, while Big ET-1, its biological precursor, has also been found elevated in breast cancer patients. In the present study, we investigated plasma ET-1 and Big ET-1 levels in patients with suspicious mammographic lesions, in order to assess their potential application as diagnostic biomarkers in the early estimation of breast disease. The study consisted of 94 patients (Group A to 30 patients with invasive ductal carcinoma: Group B, 30 with ductal carcinoma in situ; and group C, 34 with papilloma or ductal hyperplasia), who underwent an image-guided vacuum-assisted breast biopsy, and 30 healthy controls (group D). ET-1 and Big ET-1 plasma levels were measured with enzyme-linked immunosorbent assay. ET-1 levels did not exhibit significant differences between patients and healthy controls (Group A to 0.92 fmol/mL; Group B: 0.90 fmol/mL; Group C: 0.66 fmol/mL; and Group D: 0.86 fmol/mL). In contrast, Big ET-1 levels were significantly higher in patients with invasive or in situ carcinoma compared to healthy controls (Group A: 0.69 fmol/mL; Group B, 0.62 fmol/mL; and group D: 0.39 fmol/mL; p < 0.001 and p < 0.01). Plasma Big ET-1 may provide a useful tool for the early detection of invasive or noninvasive ductal breast cancer. The utilization of such a diagnostic tool would greatly assist in the modern management of breast cancer.

Endothelin-1 plasma levels and vascular endothelial dysfunction in primary open angle glaucoma

AimsTo assess the relationship between endothelial dysfunction, endothelin 1 (ET-1) plasma levels and subclinical inflammation in primary open angle glaucoma (POAG) patients. Main methodsWe enrolled 40 POAG patients with progressive visual field damage, although well controlled intraocular pressure (IOP) and compared to age and sex matched healthxy subjects. Each patient underwent an ophthalmological examination, a standard achromatic perimetry (SAP), blood sampling to assess ET-1 plasma levels, an objective assessment of cellularity within the anterior chamber (FLARE) and measurement of flow mediated dilation (FMD) with high resolution 2-dimensional ultrasonographic imaging of the brachial artery. Key findingsAt baseline, POAG patients, compared to healthy controls, showed an increase of ET-1 plasma levels: 2.83±0.28pg/ml vs. 1.75±0.25pg/ml (p<0.001), lower FMD values 4.46±1.28% vs. 13.18±2.80% (p<0.001) and increased FLARE values 9.98±0.97 photons/ms vs. 5.87±0.64 photons/ms (p<0.001). A follow up after 1year revealed a further increase of ET-1 plasma levels (to 3.68±0.60; p<0.001) and decrease of FMD (3.52±1.28; p>0.001). SignificanceThe increase of ET-1 in POAG patients is related to vascular dysfunction (r=0.942; p=0.001) and vascular dysfunction is related to sub-clinical intraocular inflammation (r=0.968; p=0.001). Thus ET-1 and vascular dysfunction related to sub-clinical inflammation may play a key role in determining a progressive visual field damage in POAG patients who present a well-controlled IOP.

Pioglitazone induces regression and stabilization of coronary atherosclerotic plaques in patients with impaired glucose tolerance

To observe the effects of pioglitazone on coronary plaque area, plaque burden, serum high-sensitivity C-reactive protein, adiponectin and plasma endothelin-1 levels in patients with impaired glucose tolerance and coronary borderline lesions. Thirty patients were randomly divided into two groups: a pioglitazone group and a control group. The latter was administered placebo in addition to standard therapy; the former pioglitazone 15 mg/d in addition to standard therapy. Before treatment and 6 months later, left ventricular ejection fraction, serum lipid profile, high-sensitivity C-reactive protein, adiponectin and plasma endothelin-1 levels were detected. Coronary plaque area and plaque burden were examined using intravascular ultrasound. No significant differences were found in left ventricular ejection fraction and serum lipid levels pre- and post-trial. Compared with the control group, 6 months' treatment with pioglitazone significantly decreased coronary plaque burden (50.7 ± 11.1 vs. 64.1 ± 10.3%, P < 0.05), plaque area (6.22 ± 2.03 vs. 8.31 ± 4.29, P < 0.05), thin-cap fibroatheroma prevalence (11 vs. 22%, P < 0.05) and percentage of necrotic core area (16 ± 8 vs. 31 ± 7%, P < 0.05). Compared with the control group, serum high-sensitivity C-reactive protein and plasma endothelin-1 levels were significantly lower and adiponectin level significantly higher in patients in the pioglitazone group. Serum adiponectin level was negatively correlated with plasma endothelin-1 level and coronary plaque area (r = 0.739 and -0.431, respectively, both P < 0.05). Pioglitazone may induce regression and stabilization of coronary atherosclerotic plaques. The mechanisms might involve inhibition of inflammation, increase in adiponectin level and improvement in endothelial function.

Haemodynamic and neuroendocrine effects of tezosentan in chronic experimental pulmonary hypertension

Chronic pulmonary hypertension (PH) therapy is poorly investigated in intensive care. Our aim was to evaluate haemodynamic and neuroendocrine effects of the dual endothelin-1 (ET-1) blocker tezosentan in monocrotaline (MCT)-induced PH. Male Wistar rats (180-200 g, n = 194) randomly received 60 mg kg(-1) MCT or vehicle, subcutaneously, and 2 days later, a subgroup of MCT-injected rats was gavaged with 300 mg kg(-1) day(-1) bosentan (MCT BOS, n = 46), while another (MCT, n = 125) and control rats (Ctrl, n = 23) received vehicle. At 25-30 days, 48 h after interrupting bosentan, rats randomly underwent either a dose-response evaluation (0.5-20 mg kg(-1), n = 7 each group) or a 4 h perfusion of tezosentan (20 mg kg(-1) in 10 min + 10 mg g(-1) h(-1)) or vehicle (n = 8 per group, each). Haemodynamics, including blood gas analysis, were evaluated after thoracotomy under anaesthesia. After plasma, right ventricle (RV) and lung collection, plasma ET-1, cytokines, nitrate and 6-keto-PGF1α, and lung and right ventricular gene expression and cyclooxygenase (COX) and nitric oxide synthase (NOS) activities were quantified. Monocrotaline resulted in PH, RV dilation and decreased cardiac output (CO) that were attenuated in MCT BOS. Pulmonary hypertension was attenuated by tezosentan without systemic hypotension. Tezosentan increased CO without changing ventilation-perfusion matching. Both bosentan and tezosentan reduced ET-1 and cytokine plasma levels and tissue expression, and inducible NOS and COX-2 RV activities. Bosentan increased nitrate plasma levels and non inducible NOS activities whereas tezosentan decreased circulating 6-keto-PGF1α but increased lung COX-1 activity. Tezosentan may be useful for haemodynamic handling and bosentan replacement in critically ill PH patients exerting important beneficial neuroendocrine and anti-inflammatory actions.

Habitual rowing exercise is associated with high physical fitness without affecting arterial stiffness in older men

The present study elucidated the effects of habitual rowing exercise on arterial stiffness and plasma levels of the vasoconstrictor endothelin-1 and the vasodilator nitric oxide (NO) in older men. Eleven rowers (68.0 ± 1.6 years) and 11 sedentary control older men (64.9 ± 1.1 years) were studied. Peak oxygen uptake (36.0 ± 1.7 vs. 27.7 ±1.9 ml · kg−1 · min−1), leg press power (1346 ± 99 vs. 1077 ± 68 W), and HDL-cholesterol (75 ± 5 vs. 58 ±3 mg · ml−1) were higher and triglyceride (78 ± 9 vs. 120 ± 14 mg · ml−1) was lower in rowers than in control participants (all P < 0.05). Arterial stiffness indices (carotid β-stiffness and cardio-ankle vascular index) and plasma endothelin-1 and NOx (nitrite + nitrate) levels did not differ between the two groups. These results suggest that habitual rowing exercise in older men is associated with high muscle power and aerobic capacity, and favourable blood lipid profile without affecting arterial stiffness or plasma levels of endotheline-1 and NO.

Relationship between baseline ET-1 plasma levels and outcome in patients with idiopathic pulmonary hypertension treated with bosentan

ObjectivesTo address if baseline endothelin-1 (ET-1) plasma levels might predict clinical worsening (CW) in patients with idiopathic pulmonary hypertension (IPAH) treated with bosentan. MethodsForty-four consecutive patients with IPAH (WHO classes II–III) were included in this study. After an initial assessment (clinical status, pulmonary hemodynamics, samples for adrenomedullin (ADM), ET-1 and brain natriuretic peptide (BNP) plasma levels), patients were treated with bosentan and followed-up for CW. ResultsWe observed CW in 24 patients. Actuarial rates of freedom from CW were 74% at 1year, 56% at 2years, and 43% at 3years. Patients with CW had a worse WHO functional class (II/III; no-CW 14/6 vs CW 5/19, p=0.002), six-minute walk-test distance (no-CW 439+94m vs CW 385+82m, p=0.04), mean pulmonary artery pressure (no-CW 47.4+10.6mm Hg vs CW 56+12.6mm Hg, p=0.02) and pulmonary vascular resistance (PVR no-CW 12.5+4.8 WU vs CW 16.4+6.3 WU, p=0.03) than the no-CW group. Moreover ET-1 (no-CW 14.1+4.2pg/ml vs CW 21.3+6.3pg/ml, p=0.0001), ADM (no-CW 14.9+7pg/ml vs CW 21.5+10.4pg/ml p=0.002) and BNP (no-CW 82.8+35.3pg/ml vs CW 115.4+39.6pg/ml, p=0.007) plasma levels were significantly higher in the CW group than in the no-CW group. The multivariate Cox proportional hazards model identified WHO class III (RR 4.6, 95%CI 14.6–1.45), ET-1 plasma levels (RR 1.1, 95%CI 2.05–1.01) and PVR (RR 1.2, 95%CI 1.3–1.03) as independent risk factors for CW. ConclusionsThese data confirm the high rate of CW in patients with IPAH treated with bosentan and document the impact of the endothelin system on CW of these patients.

Effect of isolated carotid sinus perfusion with propofol on plasma endothelin and nitric oxide levels in diabefic rats

Objective To investigate the effect of isolated carotid sinus perfusion with propofol on plasma endothelin and nitric oxide levels in diabetic rats.Methods Healthy adult Wistar rats weighing 180-220 g were used in this study.Diabetes mellitus was induced by intraperitoneal streptozotocin 30 mg/kg and confirmed by blood glucose ≥ 16.7 mmol/L.Thirty-six rats in which diabetes mellitus model was successfully established were randomly divided into 3 groups ( n =12):control group (group DC) ;low dose propofol group (group DP1 ) and high dose propofol group (group DP2 ).Another 36 non-diabetic rats were also randomly divided into 3 group ( n =12 each):control group (group NC) ; low dose propofol group group (group NP1 ) and high dose propofol (group NP2 ).After 30 min isolated carotic sinus perfusion with K-H solution (control groups),50 μmol/L propofol in K-H solution (low dose propofol groups) or 100 μmol/L propofol in K-H solution (high dose propofol groups),blood samples were taken for determination of plasma endothelin and nitric oxide concentrations.Results The plasma endothelin concentration was lower and nitric oxide concentration higher in groups DP1 and DP2 than in group DC,and in group DP1 than in group DP2 ( P ＜ 0.05).The plasma endothelin concentration was higher and nitric oxide concentration lower in group NPi than in group DP1,and in group NP2 than in group DP2 ( P ＜ 0.05 ).Conclusion Propofol can decrease endothelin level and increase nitric oxide level in diabetic or non-diabetic rats through local effect on carotid sinus,and the effect is stronger in diabetic rats than in non-diabetic rats. Key words: Propofol; Diabetes mellitus; Edothelins; Nitric oxide; Carotid sinus

Risk factors and clinical analysis on acute hepatic dysfunction induced by sepsis

Objective To study the incidence,risk factors and clinical features of patients with acute hepatic dysfunction induced by sepsis. Methods One hundred and sixty patients with sepsis were assigned to two groups according to liver function: sepsis group and acute hepatic dysfunction group. Logistic regression analysis was used to study the risk factors.The comparison of plasma endothelin-1 ( ET-1 ) and sepsis-related organ failure assessment (SOFA) score between two groups was carried out.Results Of 160sepsis patients,25 (15.6％) patients were subjected to acute hepatic dysfunction induced by sepsis.Logistic regression analysis showed that long-term indulgence in wine drunk (OR =4.102,95％ CI 1.288 -13.063 ),history of cardiac insufficiency ( OR =4.109,95％ CI 1.352 - 12.493) and hypotension ( OR =5.833,95％ CI:1.712 - 19.868 ) were the significant risk factors.Though oxygenation index ( PaO2/FiO2),platelet (PLA) and Glasgow coma scale (GCS) were not different between two groups,the total bilirubin (Tbil),direct bilirubin (Dbil),creatitine (Cre),range of blood glucose variation (Rglu),lactic acid (Lac),plasma ET-1and SOFA score in acute hepatic dysfunction group were higher than those in sepsis group. Mortality rate in acute hepatic dysfunction group was higher than that in sepsis group.Conclusions Long-term drunk,history of cardiac insufficiency and hypotension are the risk factors in acute hepatic dysfunction induced by sepsis.Elevated arterial Lac and plasma ET-1 levels,and higher SOFA score in acute hepatic dysfunction group suggest poor prognosis. Key words: Sepsis; Endothelin-1; Acute hepatic dysfunction

Effects of 29-h total sleep deprivation on local cold tolerance in humans

To study the effects of a 29-h total sleep deprivation (TSD) on local cold tolerance, 10 healthy men immersed their right hand for 30 min in a 5°C water bath (CWI) after a 30-min rest period in a thermoneutral environment (Control), after a normal night (NN) and after a 29-h TSD. CWI was followed by a 30-min passive rewarming (Recovery). Finger 2 and 4 skin temperatures (Tfi2, Tfi4) and finger 2 cutaneous vascular conductance (CVC) were monitored to study cold-induced vasodilation (CIVD). Rectal temperature (Tre), mean skin temperature ([Formula: see text]), heart rate (HR) and blood pressure (BP) were also measured. Blood samples were collected at the end of the Control, at the lower and at the first maximal Tfi2 values during CWI and at Recovery. Tfi2, Tfi4 and CVC did not differ after TSD at Control, whereas they were reduced during CWI (-2.6 ± 0.7°C for Tfi2; -2 ± 0.8°C for Tfi4, -79 ± 25% for relative CVC, P < 0.05) as during Recovery (-4.9 ± 1.9°C for Tfi2, -2.6 ± 1.8°C for Tfi4, -70 ± 22% for relative CVC, P < 0.05). After TSD, the lower CVC values appeared earlier during CWI (-59 ± 19.6 s, P < 0.05). After TSD at Control and CWI, plasma endothelin levels were higher and negatively correlated with Tfi2, Tfi4 and CVC. However, no effect of TSD was found on the number and amplitude of CIVD and in Tre, HR, BP and catecholamines, for all periods. We concluded that TSD induced thermal and vascular changes in the hand which impair the local cold tolerance, suggesting that TSD increases the risk of local cold injuries.

Endothelin-1 in systemic sclerosis

Introduction:Scleroderma is a systemic disorder with unknown etiology most notably characterized by skin thickening and organ damage. Endothelin-1 (ET-1) plays a role in skin fibrosis. The aim of this study was survey and comparison of ET-1 level in Systemic Sclerosis (SSc) patients with and without digital ulcer.Material and Methods:A cross-sectional analytical study conducted among the 95 patients with scleroderma in 2006 who were referred to the Rheumatology clinic in Shariati hospital of Tehran. The questionnaire was completed for every patient. Plasma level of endothelin-1 was also measured in all of them. The data was analyzed using SPSS software and statistical tests.Results:The result indicated, relationship among digital ulcers and digital pitting scars with plasma level of ET-1 were significant (P value < 0.05). We could not find any significant relationship between age and plasma level of ET-1.Conclusion:These data indicate plasma level of ET-1 in scleroderma patients with digital ulcer was higher than patients without digital ulcer. Thus, increase in plasma level of ET-1 could be effective in vascular damage, fibrosis, and skin thickness.

Plasma Endothelin-1 Level Is a Predictor of 10-Year Mortality in a General Population

Endothelin-1 (ET-1) is a potent vasoconstrictor and an elevated plasma level is a prognostic marker in patients with cardiovascular diseases and/or malignancies. We hypothesized that an elevated plasma level might be a prognostic marker even in subjects without apparent cardiovascular disease or malignancy at baseline. We measured plasma ET-1 levels in 1,440 healthy subjects over 40 years of age (580 men, 860 women) who were periodically followed for 10 years. The follow-up rate was 96.8%. Baseline plasma ET-1 levels were categorized into quartiles. Baseline plasma ET-1 levels were significantly associated with age, blood pressure, high-density lipoprotein-cholesterol, renal function, uric acid and all-cause death, but not with cardiovascular or cancer death. Kaplan-Meier curves demonstrated that all-cause mortality was significantly higher in the highest quartile of ET-1 than in the lowest quartile. Cox proportional hazards regression analysis demonstrated that ET-1 was an independent predictor of all-cause death [hazard ratio: 1.11, 95% confidence interval (CI) 1.01-1.23 per 1 pg/ml difference]. The hazard ratio of all-cause death in the highest quartile of plasma ET-1 (≥5.9 pg/ml) vs. the lowest quartile after adjusting for confounding factors was 1.54 (95% CI 1.09-2.20). The plasma ET-1 level may be a predictor of all-cause death in a healthy population.

Relations between Plasma von Willebrand Factor or Endothelin-1 and Restenosis following Carotid Artery Stenting

Objective: This study was designed to investigate the relation between plasma von Willebrand factor (VWF) or endothelin-1 (ET-1) and post-carotid artery stenting (CAS) restenosis. Materials andMethods: Plasma levels of VWF and ET-1 were measured in 61 patients (36 males, mean age 64.4 ± 6.8 years) before and after CAS. The mean follow-up time was 13.8 ± 1.7 months (range, 6–63). In-stent restenosis was defined as a >10% narrowing of the vascular lumen with or without ischemic symptoms following CAS. Results: In-stent restenosis was identified in 14 (23%) patients, including 3 with >50% restenosis. In the restenosis group, mean VWF and ET-1 levels at 2 weeks, 1 and 6 months after CAS were higher than the baseline levels (p < 0.05 or p < 0.01). Mean levels of VWF and ET-1 in the restenosis group were higher than in the non-restenosis group within 6 months after CAS (p < 0.05 or p < 0.01). Conclusion: Persistent elevation in plasma VWF and ET-1 within the first 6 months of CAS was found in patients with in-stent restenosis.