Plasma Endothelin-1 Concentrations Research Articles

GW24-e0022 Resistin involved in endothelial dysfunction among preclinical Tibetan male young adults

ObjectivesTo investigate the correlation of resistin and endothelial function among preclinical Tibetan male young adults.MethodsAll participants were recruited through young adults between 30 to 40-year-old with male gender in Lhasa...

Serum endothelin-1 measurement in healthy maine coon cats

The plasma concentration of endothelin (ET)-1 increases in human patients with congestive heart failure and is correlated with the degree of hemodynamic and functional changes. An increase in plasma ET-1 concentration is also correlated with cell proliferation, vasoconstriction, hypertrophy of cardi omyocytes and activation of cardiac fibroblasts, all of which are associated with clinical manifestations of heart failure (HF) and pathological remodeling of the heart. Hypertrophic cardiomyopathy (HCM) is the most commonly diagnosed heart disease in cats and is characterized by increased cardiac mass associated with concentric left ventricular hypertrophy (LVH), which is associated with mutations in the cardiac myosin binding protein C (MYBPC3) gene in Maine Coon (MC) cats. ET-1 serum concentrations were measured in 38 healthy MC cats using the human ELISA assay validated for the feline species. Unfortunately, the ET-1 values could not be assessed in the present study because they were above the maximum levels of sensitivity of the test used. ET-1 serum measurements without aprotinin in healthy MC cats is greater than values ET-1 plasma concentration with aprotinin reported by literature in healthy cats using the Biomedica Endothelin (1-21) diagnosis kit. Using this kit for serum ET-1 measurements without aprotinin in MC cats the dilution of samples is necessary.

Association Between Plasma Endothelin-1 and Severity of Different Types of Glaucoma

Endothelin-1 (ET-1) has been suggested to play an important role in the pathogenesis of glaucoma. Herein, we studied whether increased levels of plasma ET-1 are associated with changes in the visual field and changes in optical coherence tomography (OCT)-measured retinal nerve fiber layer (RNFL) thickness in patients with different types of glaucoma. : Plasma concentration of ET-1 was determined in 31 patients with primary open-angle glaucoma, 18 patients with normal tension glaucoma, 16 patients with primary angle-closure glaucoma, and in 37 normal controls. In all participants, visual field testing was performed and OCT was used to measure RNFL thickness. The correlation between mean ET-1 level and changes in the visual field (mean deviation, dB) and changes in OCT-measured RNFL thickness in 1 randomly selected eye from each patient in each group was then evaluated. The ET-1 level was 3.27±1.25 pg/mL in the primary open-angle glaucoma group (-14.09±8.76 dB), 3.12±1.46 pg/mL in the normal tension glaucoma group (-8.87±6.15 dB), 2.58±.22pg/mL in the primary angle-closure glaucoma group (-14.55±10.2 dB), and 1.53±1.49 pg/mL in the control group. Although mean ET-1 levels were significantly higher in all 3 of the glaucoma groups than in the control group, there was no significant difference in ET-1 level among the 3 glaucoma groups. In addition, no significant correlation was found between levels of plasma ET-1 and structural or functional changes in patients with different types of glaucoma. : There was no correlation between plasma levels of ET-1 and severity of glaucoma. The role ET-1 plays in the pathogenesis of glaucoma remains to be determined.

Plasma concentrations of C-nartiuretic peptide and endothelin-1 in women with essential hypertension which suffered vascular complication when inherent of different variants of angiotensin II type 1 receptor gene

Plasma concentrations of C-nartiuretic peptide and endothelin-1 in women with essential hypertension which suffered vascular complication when inherent of different variants of angiotensin II type 1 receptor gene

Biochemical Alterations and Endothelial Dysfunction in Hypercholesterolemic Rats: Effects of Bezafibrate

Background: Hypercholesterolemia is a serious problem cause biohazards for human health and endothelial dysfunction. Objective: The current study was conducted to test effects of hyperlipidemia alone or in combination with bezafibrate at various doses. Total cholesterol, triacylglecerol, high density lipoprotein (HDL), low density lipoprotein (LDL), apolipoprotein B, endothelin-1, histamine, nitric oxide (NO), IL-6, creatinine and alanine amino transferase (ALT) were assayed Methodology: Rats were randomly divided into four groups (10 rats each). The first group fed a normal diet and represents the control group. The second group fed normal diet enriched with 1% cholesterol and 5% coconut oil (cholesterol-fed group). The third group fed on normal diet and bezafibrate at a dose of 100 mg/kg/day. The fourth group is cholesterol fed and subdivided into A, B, C and supplemented with bezafibrate at various concentration 50, 100, 200 mg/kg/day respectively. Feeding was continued daily for 6 weeks after incidence of hypercholesterolemia. Results: The current study revealed that total cholesterol, triacylglycerols, apolipoprotein B, and LDL concentration were significantly elevated in the cholesterol-fed rats compared to control alone and control plus bezafibrate. In addition, plasma endothelin-1, histamine and IL-6 concentration were significantly elevated in the cholesterol-fed rats compared to bezafibrate and control group rats. Bezafibrate administration to rats fed high cholesterol diet normalized significantly the changes in all parameters except NO levels compared to hyperlipidemic group. Meanwhile, the plasma nitric oxide in all groups was not significantly different from those of control. However, plasma HDL concentration in the cholesterol fed rats was significantly lowered compared to bezafibrate treated rats. Conclusion: Bezafibrate may acts as a mixed blessing drug to normalize lipid profiles and endothelial dysfunction during hyperlipidemia. © 2013 GESDAV

Sodium Nitrate Supplementation Does Not Enhance Performance of Endurance Athletes

Supplementation with inorganic nitrate has been suggested to be an ergogenic aid for athletes as nitric oxide donor. The purpose of this study was to determine whether ingestion of inorganic sodium nitrate benefits well-trained athletes performing a 40-min exercise test in laboratory conditions. In addition, we investigated the effect of this supplement on plasma levels of endothelin-1 (ET-1) and in nitrated proteins. Thirteen trained athletes participated in this randomized, double-blind, crossover study. They performed a 40-min cycle ergometer distance-trial test after two 3-d periods of dietary supplementation with sodium nitrate (10 mg·kg of body mass) or placebo. Concentration of plasma nitrate (256 ± 35 μM) and nitrite (334 ± 86 nM) increased significantly (P < 0.05) after nitrate supplementation compared with placebo (nitrate: 44 ± 11 μM; nitrite: 187 ± 43 nM). In terms of exercise performance, there were no differences in either the mean distance (nitrate: 26.4 ± 1.1 km; placebo: 26.3 ± 1.2 km; P = 0.61) or mean power output (nitrate: 258 ± 28 W; placebo: 257 ± 28 W; P = 0.89) between treatments. Plasma ET-1 increased significantly (P < 0.05) just after exercise in nitrate (4.0 ± 0.8 pg·mL) and placebo (2.4 ± 0.4 pg·mL) conditions. This increase was significantly greater (P < 0.05) in the nitrate group. Levels of nitrated proteins did not differ between treatments (nitrate: preexercise, 91% ± 23%; postexercise, 81% ± 23%; placebo: preexercise, 95% ± 20%; postexercise, 99% ± 19%). Sodium nitrate supplementation did not improve a 40-min distance-trial performance in endurance athletes. In addition, concentration of plasma ET-1 increased significantly after exercise after supplementation with sodium nitrate.

Correlation of Endothelin-1 Concentration in Aqueous Humor with Intraocular Pressure in Primary Open Angle and Pseudoexfoliation Glaucoma

Endothelin-1 (ET-1) has been found in elevated concentrations in the aqueous humor of glaucoma patients. Indirect evidence from animal studies suggests that ET-1 might directly influence intraocular pressure (IOP). The aim of this study was to determine whether ET-1 concentrations in aqueous humor of cataract and glaucoma patients correlate with IOP. Aqueous humor and blood samples from patients with either cataract (control, n = 38), primary open angle glaucoma (POAG, n = 35), or pseudoexfoliation glaucoma (PEXG, n = 21), without other ocular or systemic disease, were collected during routine cataract surgery or trabeculectomy. ET-1 concentration was determined by an ET-1 ELISA kit. IOP was measured preoperatively by standard Goldmann applanation tonometry. All statistical analysis was performed using commercial predictive analytics software. Both IOP and ET-1 concentration in aqueous humor were significantly increased in POAG (23.4 ± 6.8 mm Hg, 5.9 ± 2.9 pg/mL) and PEXG (24.3 ± 8.8 mm Hg, 7.7 ± 2.1 pg/mL) compared with control (15.0 ± 2.9 mm Hg, 4.3 ± 2.4 pg/mL). No difference was detected for plasma ET-1 concentrations. IOP and ET-1 in the aqueous humor were significantly correlated (R = 0.394, R² = 0.155, P < 0.001), although no correlation was found between IOP and ET-1 in blood plasma or between ET-1 in aqueous humor and ET-1 in plasma. In this study, a small but highly significant correlation between IOP and the ET-1 concentration in the aqueous humor was found. Although no causative relationship can be deduced from this, ocular ET-1 effects on IOP control may merit further investigation.

Competitive flow arising from varying degrees of coronary artery stenosis affects the blood flow and the production of nitric oxide and endothelin in the internal mammary artery graft

Internal mammary arteries graft failure in coronary artery bypass grafting (CABG) is mostly considered to be a result of competitive flow (CF) from the native coronary artery, which significantly limits future revascularization options. With the left internal mammary artery (LIMA) anastomosed to the left anterior descending (LAD) coronary artery using an off-pump technique, CABG was performed on 15 Chinese swine. Then we produced varying degrees of stenosis in the proximal LAD coronary artery with an adjustable flow occluder, measured the mean flow of the LIMA and LAD coronary artery and detected the plasma concentrations of nitric oxide (NO) and endothelin (ET) in the LIMA graft. When stenosis of the proximal LAD artery was decreased, the CF of the native LAD coronary artery showed an increasing trend, while the mean flow of the LIMA revealed a decreasing trend. Distal LAD coronary artery flow remained nearly constant, despite the varying proximal LAD artery or LIMA flow rates. An oscillating flow pattern (retrograde/antegrade) was noted in the LIMA graft when the proximal LAD coronary artery was not fully occluded. The plasma concentration of ET in the LIMA graft was significantly higher than that before grafting (P < 0.05), and the plasma concentration of NO was significantly lower (P < 0.05). The concentration of NO was positively related to the mean flow in the LIMA (r = 0.872, P < 0.05). CF from the native LAD coronary artery can decrease the blood flow in the LIMA graft and even change the direction of the flow. These changes may impair the function of the LIMA graft and affect ET or NO production, which in turn may lead to early LIMA graft failure.

Effects of Short-Term Forest Bathing on Human Health in a Broad-Leaved Evergreen Forest in Zhejiang Province, China

ObjectiveTo investigate the effects of short-term forest bathing on human health. MethodsTwenty healthy male university students participated as subjects and were randomly divided into two groups of 10. One group was sent on a two-night trip to a broad-leaved evergreen forest, and the other was sent to a city area. Serum cytokine levels reflecting inflammatory and stress response, indicators reflecting oxidative stress, the distribution of leukocyte subsets, and plasma endothelin-1 (ET-1) concentrations were measured before and after the experiment to evaluate the positive health effects of forest environments. A profile of mood states (POMS) evaluation was used to assess changes in mood states. ResultsNo significant differences in the baseline values of the indicators were observed between the two groups before the experiment. Subjects exposed to the forest environment showed reduced oxidative stress and pro-inflammatory level, as evidenced by decreased malondialdehyde, interleukin-6, and tumor necrosis factor a levels compared with the urban group. Serum cortisol levels were also lower than in the urban group. Notably, the concentration of plasma ET-1 was much lower in subjects exposed to the forest environment. The POMS evaluation showed that after exposure to the forest environment, subjects had lower scores in the negative subscales, and the score for vigor was increased. ConclusionForest bathing is beneficial to human health, perhaps through preventive effects related to several pathological factors.

Vasomodulating function of the endothelium in hemorrhagic fever with renal syndrome

Aim. To study the content of endothelin-1, nitric oxide (II) and the activity of angiotensin-converting enzyme in the blood of patients with hemorrhagic fever with renal syndrome, depending on the period and the severity of the disease in order to assess their role in the pathogenesis and to develop a pathogenetically substantiated correction of the changes in the systemic vascular tone. Methods. The group of dynamic study included 114 patients (102 male and 12 female) with serologically confirmed hemorrhagic fever with renal syndrome aged 22-55 years. The moderately severe form was diagnosed in 66 patients, severe uncomplicated form - in 27, severe form with complications - in 21 patients. The control group comprised 23 practically healthy volunteers. The concentration of endothelin-1 in blood plasma, the contents of metabolic products of nitric oxide (II) and the activity of the angiotensin-converting enzyme in the blood serum were determined. Results. The concentration of endothelin-1 in the blood in the dynamics of the disease significantly decreased, the content of the final stable metabolites of nitric oxide (II) and the activity of the angiotensin-converting enzyme increased with statistical significance in all periods of the disease. These changes were most pronounced during severe forms of the disease with complications. Conclusion. In moderately severe and severe uncomplicated forms of the disease the endothelium is able to maintain the systemic vascular tone and tissue perfusion at a physiological level, however in severe form with complications the changes in the synthesis of vasomodulating substances may be involved in the development of complications.

The Relationships Between Plasma Adrenomedullin and Endothelin-1 Concentrations and Doppler Echocardiographic Indices of Left Ventricular Function During Static Exercise in Healthy Men

Our previous study showed a significant relationships between static exercise-induced changes in plasma adrenomedullin (ADM) and those in endothelin-1 (ET-1), noradrenaline (NA) and pre-ejection period/left ventricular ejection time ratio (PEP/LVET) in older healthy men. It is hypothesized that ADM, ET-1, NA and adrenaline (A) may function as endogenous regulators of cardiac function by modulating myocardial contractility during static exercise. The present study was undertaken to assess the relationships between exercise-induced changes in plasma ADM, ET-1, NA, A concentrations and those in ascending aortic blood flow peak velocity (PV) and mean acceleration (MA) measured by Doppler echocardiography in 24 healthy older men during two 3-min bouts of handgrip at 30% of maximal voluntary contraction, performed alternately with each hand without any break between the bouts. Plasma ADM, ET-1, NA and A as well as heart rate (HR), blood pressure (BP), PV and MA were determined. During handgrip, plasma ADM, ET-1, NA and A as well as HR, BP increased, whereas PV and MA decreased. The increases in plasma ADM correlated positively with those in ET-1, NA and diastolic BP, and correlated negatively with changes in PV (r= −0.68) and MA (r= −0.62). The increases in plasma ET-1 correlated positively with those in NA and BPs and correlated negatively with changes in PV (r= −0.67) and MA (r= −0.60). The results of this study suggest that in healthy older men the exercise-induced changes in plasma ADM, ET 1 and catecholamines are related to alterations in left ventricular contractile state and may co-operatively counteract age-related deterioration of cardiac performance in men.

Simvastatin attenuated cerebrovascular cell proliferation in the development of hypertension through Rho/Rho-kinase pathway.

The cerebrovascular remodeling is a prominent feature of hypertension and considered as a major risk of stroke. Statins may suppress the activation of the Rho/Rho-kinase pathway and have pleiotropic actions against the development of vascular remodeling. We hypothesized that the inhibition of the Rho/Rho-kinase pathway by simvastatin during hypertension could recuperate the pathological changes of basilar artery through the downregulation of cell proliferation. To resolve the problem, we used 2-kid, 2-clip rat as a hypertension model and evaluated the effect of simvastatin on the Rho/Rho-kinase pathway. In addition, we assessed the changes of the proliferation rate by CCK-8 assay in basilar artery smooth muscle cells. Our results from this study showed that a continuous increase in the plasma endothelin-1 (ET-1) concentration and the Rho/Rho-kinase activity was positively correlated with changes in blood pressure in the hypertensive rat. Simvastatin ameliorated the upregulated Rho/Rho-kinase activity and cell proliferation during hypertension. Moreover, simvastatin, the RhoA inhibitor C3, and the RhoA-kinase inhibitor Y27632 all attenuated the proliferation rate induced by ET-1 in basilar artery smooth muscle cells via the Rho/Rho-kinase signaling pathway. In conclusion, simvastatin attenuated ET-1-induced proliferation through the Rho/Rho-kinase signaling pathway in hypertensive rat basilar artery, and it may be an excellent reagent to protect vascular remodeling and stroke.

Effects of high-intensity and blood flow-restricted low-intensity resistance training on carotid arterial compliance: role of blood pressure during training sessions

We examined the effects of high-intensity resistance training (HIT) and low-intensity blood flow-restricted (LI-BFR) resistance training on carotid arterial compliance. Nineteen young men were randomly divided into HIT (n = 9) or LI-BFR (n = 10) groups. The HIT and LI-BFR groups performed 75 and 30 %, respectively, of one-repetition maximum (1-RM) bench press exercise, 3 days per week for 6 weeks. During the training sessions, the LI-BFR group wore elastic cuffs around the most proximal region of both arms. Muscle cross-sectional area (CSA), 1-RM strength, and carotid arterial compliance were measured before and 3 days after the final training session. Acute changes in systolic arterial pressure (SAP), plasma endothelin-1 (ET-1), nitrite/nitrate (NOx), and noradrenalin concentrations were also measured during and after a bout of training session. The training led to significant increases (P < 0.01) in bench press 1-RM and arm and chest muscle CSA in the two training groups. Carotid arterial compliance decreased significantly (P < 0.05) in the HIT group, but not in the LI-BFR group. There was a significant correlation (r = -0.533, P < 0.05) between the change in carotid arterial compliance and the acute change in SAP during training sessions; however, ET-1 and NOx did not correlate with carotid arterial compliance. Our results suggest that muscle CSA and strength increased following 6 weeks of both HIT and LI-BFR training. However, carotid arterial compliance decreased in only the HIT group, and the changes were correlated with SAP elevations during exercise sessions.

Endothelin‐1 derived from spleen‐activated Rho‐kinase pathway in rats with secondary biliary cirrhosis

Splenectomy or partial splenic embolism has been reported to improve liver function in patients with hypersplenism and liver dysfunction. The aim of this study was to investigate the mechanism of improvement after splenectomy. Liver cirrhosis was induced by bile duct ligation (BDL). Rats underwent sham operation, splenectomy (Sp group), BDL, or BDL plus splenectomy (BDL + Sp group), and were subjected to experiments at 2 weeks after the operation. Portal venous pressure (PVP) and hepatic tissue blood flow (HTBF) were measured in each group. The plasma concentration of endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS), RhoA and Rho-kinase expressions were studied. There were significant differences in PVP (17.9 ± 0.91 vs 23.3 ± 3.91 cmH(2) O; P < 0.01) and HTBF (16.6 ± 1.72 vs 13.3 ± 1.82 mL/min; P < 0.01) between the BDL + Sp and BDL groups. In the liver of BDL rats, eNOS phosphorylation and NOx levels were decreased, accompanied by RhoA activation compared with the BDL + Sp group. Splenectomy decreased serum ET-1 levels, RhoA activation and consequently increased eNOS phosphorylation. ET-1 derived from the spleen might increase intrahepatic resistance by downregulating Rho signaling in liver cirrhosis. Splenectomy for splenomegaly in liver cirrhosis might partially improve liver function by enhancing intrahepatic microcirculation.

Endothelin-1 and Adrenomedullin Plasma Levels After Exposure to Fludrocortisone, Dexamethasone, and Spironolactone

We asked whether plasma concentrations of endothelin-1 (ET-1) or adrenomedullin (ADM) are altered by different activity states of the renin–angiotensin–aldosterone system (RAAS). Levels of ET-1 and ADM were studied in patients with primary aldosteronism (n = 15), essential hypertension (n = 15), and adrenal insufficiency (n = 7). Effects of fludrocortisone, dexamethasone, or spironolactone treatment on ET-1 and ADM levels were also analyzed. Plasma ET-1 and ADM concentrations did not differ significantly between the patient groups. After fludrocortisone, dexamethasone, or spironolactone treatment, both ET-1 and ADM did not change significantly. The data support the hypothesis that the RAAS is not directly linked with the ET-1/ADM system.

Resistin involved in endothelial dysfunction among preclinical Tibetan male young adults

Resistin, an adipocyte-derived hormone, was found to be linked to metabolic syndrome and insulin resistance over the past decade. There is growing evidence that resistin plays a potential role in endothelial dysfunction. To the best of our knowledge, few studies have been concerned with the effect of resistin on endothelial function in a Tibetan population. To investigate the correlation of resistin and endothelial function among preclinical Tibetan male young adults. All participants recruited were young adults between 30 and 40 years old of male gender in Lhasa city. All subjects were native Tibetan. A total of 90 healthy subjects were accepted after excluding hypertension, diabetes, hyperlipidemia or coronary artery disease. The subjects were divided into three groups according to flow-mediated dilation (FMD): lower FMD (group A), intermediate FMD (group B) and higher FMD (group C). Body mass index, systolic blood pressure (SBP), diastolic blood pressure (DBP) and cigarette smoking were evaluated. Venous blood was sampled for the measurement of lipid profile, fasting blood glucose (FBG), fasting insulin (FINS), endothelin-1 (ET-1) and plasma resistin quantitation. The non-invasive vascular endothelial function was evaluated through the measurement of FMD with B-mode ultrasound. The insulin resistance was estimated as homeostatic model assessment of insulin resistance (HOMA-IR) = FINS(mu/L)*FBG(mmol/L)/22.5. No statistical significance was found between groups in age, smoking, SBP, DBP, fasting insulin, total cholesterol and HOMA-IR (p>0.05). In the lipid profile, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol in group C were better than in groups A and B (p<0.01). Body mass index, which is an indicator for obesity, was much lower in group C than in group A and B (p<0.05 and 0.01 respectively). Comparison of plasma resistin concentrations: group A > group B > group C (p<0.01). Comparison of plasma ET-1 concentrations had a similar result: group A > group B > group C (p<0.05). The multivariate regression analysis showed that total cholesterol (p<0.05), LDL cholesterol (p<0.01), plasma resistin (p<0.01) and plasma ET-1 (p<0.01) were correlated with FMD. Resistin is involved in endothelial dysfunction in preclinical male young Tibetan adults.

Sympathetic and vascular dysfunction in adult patients with Fontan circulation

BackgroundPatients with Fontan circulation are known to have increased systemic vascular resistance (SVR) however the underlying mechanisms are uncertain. We therefore further investigated the haemodynamic and vascular profile of Fontan patients. MethodsEighteen adult subjects aged 25±1years who had undergone the Fontan procedure in their childhood (at age 6±1years) and not in clinical failure at the time of study were assessed for: 1) autonomic function, including direct muscle sympathetic nerve activity (MSNA) recording and sympathetic and cardiac baroreflex function, 2) endothelial function by means of reactive hyperaemia using the Endopat peripheral arterial tonometry (PAT) technique and plasma endothelin concentration and gene expression, 3) pulse wave reflections (digital and central augmentation index (AI)) and 4) haemodynamic changes to head-up tilt. Data were compared to that obtained in a group of 23 age- and weight-matched healthy subjects. ResultsFontan participants presented with elevated MSNA compared with controls (40±5 vs 27±3 bursts per 100 heartbeats), decreased cardiac baroreflex function (16.0±3.3 versus 30.9±3.7ms·mm Hg−1), normal sympathetic baroreflex function, decreased endothelial function (PAT ratio=0.35±0.09 vs 0.77±0.11), and increased digital (5.9±3.0% vs −9.7±2.3%) and central (1.4±2.7% vs −10.2±3.9%) AI. Ten minute head-up tilt (60°) induced greater reductions in cardiac output (CO) and stroke volume (SV) in Fontan patients (CO: −28% vs −11%, SV: −40% vs −25%). ConclusionAdult Fontan patients have increased MSNA and altered endothelial function that are likely to contribute to their known increased SVR. Therapies aiming at reducing the peripheral resistances should target endothelial function and sympathetic activity.

Endothelial biomarkers as indicators of cardiovascular complications in young patients with arterial hypertension

This study evaluated nitric oxide (NO) and endothelin‐1 (ET‐1) as clinically relevant biomarkers in young patients with early arterial hypertension (AH). Male patients (n=65, 20–45 years of age) with AH duration &lt;6 years and blood pressure (BP) &lt;160/100 mm Hg were studied. A control group consisted of 32 age‐matched healthy subjects. Endothelium‐dependent vasodilation (EDVD) was evaluated by measuring post‐occlusion reactive hyperemia in the brachial artery. NO production was evaluated by plasma concentration and 24‐hour urinary excretion of nitrite + nitrate. Plasma concentration of ET‐1 was measured by immunoenzyme assay. The plasma NO/ET‐1 ratio was calculated. EDVD was 12.3% lower in patients with AH than in healthy subjects, and this decrease correlated with the duration of AH. The NO/ET‐1 ratio was significantly lower in the AH group (2.0±0.4 vs 6.2±0.6, p&lt;0.001), and the NO/ET‐1 ratio decreased with AH duration. NO/ET‐1 values below 3.0 were associated with atypical diurnal BP profile and cardiac arrhythmias. NO/ET‐1 values below 1.0 were associated with severe cardiovascular complications. Thus, the ratio of NO to ET‐1 appears to be a useful marker for cardiovascular complications in young patients with arterial hypertension.

Deterioration of endothelial function and carotid intima-media thickness in Tibetan male adolescents exposed to second-hand smoke

It has been commonly accepted that second-hand smoke (SHS) is associated with atherosclerosis and endothelial dysfunction. There is growing evidence that the changes might begin in childhood. Unfortunately, no study has focused on the early atherosclerosis of Tibetan adolescents exposed to SHS. We aimed to investigate the endothelial function and carotid atherosclerosis in healthy school-aged Tibetan male adolescents. All passive smoking participants (SHS) were students were 16 years old and male, and were recruited through middle schools in Lhasa city. In total 624 subjects were accepted after excluding subjects who actively smoked. The adolescents were divided into three groups according to serum cotinine level: high cotinine group (High Group) with 205 boys, intermediate cotinine group (Intermediate Group) with 210 boys, and low cotinine group (Low Group) with 209 boys. Venous blood was sampled for the measurement of cotinine concentration, lipid profile and endothelin-1 (ET-1) quantitation. High-resolution B-mode ultrasonography was performed to evaluate carotid intima-media thickness (cIMT) and intima smoothness. The invasive vascular endothelial function was evaluated through the measurement of flow-mediated dilation (FMD) with B-mode ultrasound and ankle-brachial index (ABI) by using a blood pressure cuff and a Doppler instrument. No statistical significance was found between groups in total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, ApoA-I, systolic blood pressure, diastolic blood pressure, and heart rate (p>0.05). In the lipid profile, only apolipoprotein B (ApoB) values were different between groups: ApoB in the High Group was higher than in the Low Group (p=0.0164). Plasma ET-1 concentrations in the High Group were also much higher than in the Intermediate and Low Groups (p=0.0112, p<0.001). The cIMT and intima smoothness had deteriorated in the High Group compared with the Low Group (p<0.001 and p<0.05 respectively). FMD and ABI, which indicate vascular endothelial function, was decreased in the High Group compared with the Intermediate and Low Groups (FMD, p<0.001; ABI, p<0.001). SHS was associated with sub-clinical carotid atherosclerosis and endothelial dysfunction in Tibetan school-aged male adolescents. Considering the widespread exposure to SHS and the clinical relevance of early atherosclerosis, this result is of public health importance in Tibet, where health education is not satisfactory. Data from our study emphasize the importance of endorsing smoke-free environments for adolescents.

Increased endothelin-1 vasoconstriction in mesenteric resistance arteries after superior mesenteric ischaemia-reperfusion.

Endothelin-1 (ET-1) plays an important role in the maintenance of vascular tone. We aimed to evaluate the influence of superior mesenteric artery (SMA) ischaemia-reperfusion (I/R) on mesenteric resistance artery vasomotor function and the mechanism involved in the changes in vascular responses to ET-1. SMA from male Sprague-Dawley rats was occluded (90 min) and following reperfusion (24h), mesenteric resistance arteries were dissected. Vascular reactivity was studied using wire myography. Protein and mRNA expression, superoxide anion (O(2) (•-) ) production and ET-1 plasma concentration were evaluated by immunofluorescence, real-time quantitative PCR, ethidium fluorescence and elisa, respectively. I/R increased ET-1 plasma concentration, ET-1-mediated vasoconstriction and ET(B) mRNA expression, and down-regulated ET(A) mRNA expression. Immunofluorescence confirmed mRNA results and revealed an increase in ET(B) receptors in the mesenteric resistance artery media layer after I/R. Therefore, the ET(B) receptor agonist sarafotoxin-6 induced a contraction that was inhibited by the ET(B) receptor antagonist BQ788 only in vessels, with and without endothelium, from I/R rats. Furthermore, BQ788 potentiated ET-1 vasoconstriction only in sham rats. Endothelium removal in rings from I/R rats unmasked the inhibition of ET-1 vasoconstriction by BQ788. Endothelium removal, N(ω) -nitro-L-arginine methyl ester and superoxide dismutase abolished the differences in ET-1 vasoconstriction between sham and I/R rats. We also found that I/R down-regulates endothelial NOS mRNA expression and concomitantly enhanced O(2) (•-) production by increasing NADPH oxidase 1 (NOX-1) and p(47phox) mRNA. Mesenteric I/R potentiated the ET-1-mediated vasoconstriction by a mechanism that involves up-regulation of muscular ET(B) receptors and decrease in NO bioavailability.