The involvement of nitric oxide and endothelin-1 in exercise-induced bronchospasm in young soccer players.

OBJECTIVES: To investigate the levels of nitric oxide (NO) and endothelin-1 (ET-1) in soccer players with exercise-induced bronchospasm (EIB), to test whether these endogenous vasoactive molecules are involved in the development of EIB, and to examine the possible participation of reactive oxygen metabolites in these alterations. DESIGN: Observational study. SETTING: Football club. PARTICIPANTS: Forty-three soccer players (N = 43) aged 16 to 22 years performed maximal exercise test on a treadmill by using Bruce protocol. INTERVENTIONS: Respiratory function tests were evaluated before and after exercise tests. Participants were grouped as control (n = 35) or EIB (n = 8) groups according to the respiratory function test results. MAIN OUTCOME MEASURES: Endothelin-1 (ET-1), nitric oxide (NO), carbonyl, malondialdehyde, and glutathione levels were determined from the blood samples taken before and after exercise tests. RESULTS: In the control group, significant decreases in plasma ET-1 and serum NO levels were determined after exercise. On the other hand, plasma malondialdehyde and carbonyl levels were significantly decreased, whereas glutathione levels were significantly increased after exercise. In the EIB group, blood levels of NO, ET-1, carbonyl, and malondialdehyde after exercise were found to be significantly increased compared with pre-exercise levels. CONCLUSIONS: These findings demonstrate that in young soccer players, EIB is associated with elevated serum NO and plasma ET-1 levels. Moreover, significant increases in lipid peroxidation and protein oxidation and decreases in antioxidant sulfhydryl (RSH) content indicate a significant compromise in the blood antioxidant status and the presence of systemic oxidative stress in young athletes with EIB.

Extremely low-frequency electromagnetic fields affect the immune response of monocyte-derived macrophages to pathogens.

This study aimed to determine the effect of extremely low-frequency electromagnetic fields (ELF-EMF) on the physiological response of phagocytes to an infectious agent. THP-1 cells (human monocytic leukemia cell line) were cultured and 50 Hz, 1 mT EMF was applied for 4-6 h to cells induced with Staphylococcus aureus or interferon gamma/lipopolysaccharide (IFγ/LPS). Alterations in nitric oxide (NO), inducible nitric oxide synthase (iNOS) levels, heat shock protein 70 levels (hsp70), cGMP levels, caspase-9 activation, and the growth rate of S. aureus were determined. The growth curve of exposed bacteria was lower than the control. Field application increased NO levels. The increase was more prominent for S. aureus-induced cells and appeared earlier than the increase in cells without field application. However, a slight decrease was observed in iNOS levels. Increased cGMP levels in response to field application were closely correlated with increased NO levels. ELF-EMF alone caused increased hsp70 levels in a time-dependent manner. When cells were induced with S. aureus or IFγ/LPS, field application produced higher levels of hsp70. ELF-EMF suppressed caspase-9 activation by a small extent. These data confirm that ELF-EMF affects bacterial growth and the response of the immune system to bacterial challenges, suggesting that ELF-EMF could be exploited for beneficial uses.

Do N-Terminal Pro-C-Type Natriuretic Peptide Levels Relate to Severity of Preeclampsia?

AIM: To compare the plasma N-terminal pro-C-type natriuretic peptide concentrations of normotensive pregnant women, patients with mild preeclampsia, and patients with severe preeclampsia. METHODS: We collected venous blood samples from 25 normotensive pregnant women, 15 patients with mild preeclampsia, and 15 patients with severe preeclampsia. The women were at 30th to 40th weeks of gestation and in an age range of 20 to 35. The N-terminal pro-C-type natriuretic peptide levels were measured by ELISA. Statistical comparisons were made by one-way analysis of variance, Kruskal-Wallis, and Mann-Whitney U tests. RESULTS: The median (interquartile range-IQR) values of the N-terminal pro-C-type natriuretic peptide were 6.48 (3.33) pmol/L in the normotensive women group, 7.37 (3.43) pmol/L in patients with mild preeclampsia, and 11.52 (6.13) pmol/L in patients with severe preeclampsia. The N-terminal pro-C-type natriuretic peptide was significantly elevated in the severe preeclampsia study group (P < 0.001), whereas there was no significant difference between those with mild preeclampsia and the normotensive groups (P > 0.05). CONCLUSION: Our data indicate that the plasma concentration of the N-terminal pro-C-type natriuretic peptide is significantly increased in patients with severe preeclampsia, but not in patients with mild preeclampsia. The severity of preeclampsia may be related to the circulating levels of the N-terminal pro-C-type natriuretic peptide concentrations.

Comparison of the usage of intravenous iloprost and nitroglycerin for pulmonary hypertension during valvular heart surgery.

BACKGROUND: Pulmonary hypertension secondary to valvular heart disease is a cause of acute right heart failure during valve replacement operations. This study compares the hemodynamic effects of intravenous use of iloprost and nitroglycerin in patients with pulmonary hypertension undergoing valvular replacement surgery. We sought to determine the acceptable doses of these medications for use in surgery to decrease mean pulmonary artery pressure to <30 mmHg without causing systemic side effects. The plasma nitric oxide levels that were obtained from pulmonary mixed venous blood have been compared to demonstrate the difference in the action mechanism of these drugs. METHODS: Eighteen patients undergoing mitral or aortic and mitral valvular replacement with pulmonary hypertension >25 mmHg were included in the study. The 2 groups received iloprost or nitroglycerin via a central pulmonary catheter, and the hemodynamic parameters were evaluated before incision (T1), 10 minutes after chest opening (T2), and 5 minutes and 20 minutes after cardiopulmonary bypass (T3 and T4). The plasma nitric oxide levels were obtained from the mixed venous blood at the T1 and T4 intervals. RESULTS: The data have been analyzed for each group and for repeated measurements of hemodynamic parameters at T1-T4 time points. The analysis of hemodynamic parameters before (T1 and T2) and after (T3 and T4) bypass showed similar responses depending on the use of either iloprost or nitroglycerin. The administration of iloprost after bypass (T3) at a dosage of 1.25 to 2.5 ng/kg per minute reduced mean pulmonary artery pressure (from 28.8 +/- 7.89 to 20.63 +/- 6.39 mmHg) and pulmonary vascular resistance (from 226.88 +/- 101.93 to 118.00 +/- 82.36 dyn sec cm -5) better than nitroglycerin at a dosage of 0.5 to 1 microg/kg per minute (from 23.20 +/- 5.20 to 18.50 +/- 5.10 mmHg and from 160.80 +/- 39.76 to 137.40 +/- 56.54 dyn sec cm -5, respectively). Iloprost causes significant increase in cardiac output (from 4.91 +/- 0.91 to 5.49 +/- 0.91 L/min) compared to nitroglycerin (from 5.23 +/- 0.80 to 5.27 +/- 0.74 L/min). The plasma nitric oxide levels of the iloprost group did not show an increase from T1 to T4, whereas the nitroglycerin group levels did (P <.05). CONCLUSIONS: Intravenous use of both iloprost and nitroglycerin effectively reduces mean pulmonary artery pressure, although only the iloprost group was accompanied by an increase in cardiac output. During operation, where abrupt management of pulmonary hypertension is required, systemic use of iloprost or nitroglycerin at appropriate doses via a pulmonary artery catheter offers adequate relief of hypertension and is well tolerated without any significant adverse effects. The plasma nitric oxide levels did not rise with the use of iloprost.

Nitric oxide, endothelin-1, and superoxide production in arterial bypass grafts.

In this study, basal and thrombin-stimulated release of nitric oxide and endothelin-1 in the internal mammary artery and the radial artery were measured, together with superoxide radicals generated after anoxia and reoxygenation. Arterial segments were obtained from patients undergoing coronary bypass operations. Quantification of nitric oxide was performed by measuring the stable oxidation products of nitric oxide. Endothelin levels were measured by an enzyme immunoassay kit, and the superoxides were measured by lucigenin-enhanced chemiluminescence. Basal and stimulated release of nitric oxide from the internal mammary artery is significantly higher than that in the radial artery. On the other hand, basal release of endothelin-1 is less in the internal mammary artery than in the radial artery, but similar after stimulation. In our study, the quantity of superoxide radicals produced by the internal mammary artery was greater than that produced by the radial artery. Our results show that there are differences between these 2 arteries in regard to production of nitric oxide, endothelin-1, and superoxide radicals. These differences may have a role in the process of atherogenesis and may contribute to long-term patency of arterial bypass grafts. These results may also explain the mechanism of radial artery graft spasm in coronary artery surgery and may constitute a basis for future pharmacological and clinical improvements for successful surgical application.

Obestatin improves ischemia/reperfusion-induced renal injury in rats via its antioxidant and anti-apoptotic effects: role of the nitric oxide.

Obestatin was shown to have anti-inflammatory effects in several inflammatory models. To elucidate the potential renoprotective effects of obestatin, renal I/R injury was induced in male Sprague Dawley rats by placing a clamp across left renal artery for 60min following a right nephrectomy. Clamp was released and the rats were injected with either saline or obestatin (10, 30, 100µg/kg). In some experiments, obestatin (10µg/kg) was administered with L-NAME (10mg/kg) or L-Nil (0.36mg/kg). Following a 24-h reperfusion, the rats were decapitated to measure serum creatinine and nitrite/nitrate levels, renal malondialdehyde (MDA), glutathione (GSH) levels and myeloperoxidase (MPO) activity and to assess cortical necrosis and apoptosis scores. Obestatin treatment reduced I/R-induced increase in creatinine levels, renal MPO activity and renal MDA levels, while renal GSH levels were significantly increased by obestatin. Histological analysis revealed that severe I/R injury and high apoptosis score in the kidney samples of saline-treated rats were significantly reduced and the cortical/medullary injury was ameliorated by obestatin. Expression of eNOS, which was increased by I/R injury, was further increased by obestatin, while serum NO levels were significantly decreased. iNOS inhibitor L-Nil reduced oxidative renal damage and improved the functional and histopathological parameters. I/R-induced elevation in eNOS expression, which was further increased by obestatin, was depressed by L-NAME and L-Nil treatments. The present data demonstrate that obestatin ameliorates renal I/R-injury by its possible anti-oxidative, anti-inflammatory and anti-apoptotic properties, which appear to involve the suppression of neutrophil accumulation and modulation of NO metabolism.

Diet-supported aerobic exercise reduces blood endothelin-1 and nitric oxide levels in individuals with impaired glucose tolerance.

BACKGROUND: Impaired glucose tolerance (IGT) forms an intermediate stage in the natural history of diabetes mellitus. Insulin-resistant states might be associated with dysfunction of the vascular endothelium. OBJECTIVES: To determine the effects of chronic exercise and a low-calorie diet on plasma nitric oxide (NO) and endothelin-1 (ET-1) levels in patients with IGT and to elucidate the relationship between the oxidant stress markers and NO/ET-1 levels of blood before and after exercise. METHODS: Patients with IGT (n = 14) participated in a regular exercise program and exercised for 40 minutes each day, 3 days a week for 12 weeks. Physiological, anthropometric, and biochemical measurements were performed before, during the 6th week, and at the end of the program. RESULTS: There was a significant reduction in body mass index, body fat content, systolic and diastolic blood pressures, as well as NO and ET-1 concentrations after 12 weeks of exercise and diet program. Exercise training significantly elevated subjects' maximum oxygen consumption, whereas the resting metabolic rates of the patients did not change. The formation of thiobarbituric acid reactive substances were significantly reduced, whereas sulfhydryl groups were significantly increased on the 6th week (P < .05) and at the end of program (P < .01). CONCLUSION: Our results demonstrate that exercise, along with low-calorie diet, induced reductions in the plasma of both ET-1 and NO. Beneficial effects were observed on anthropometric measurements and plasma oxidant stress markers, indicating weight loss associated with exercise training and calorie restriction may effectively improve endothelial dysfunction in patients with IGT.

The relation between blood and tissue magnesium levels and development of atrial fibrillation after coronary artery bypass surgery.

OBJECTIVE: Atrial fibrillation (AF) is a common complication of cardiovascular surgery and its mechanisms are not well understood. The aim of our study was a prospective investigation of the relationship between AF development and tissue or blood magnesium levels. METHODS: This prospective observational study evaluated 20 patients undergoing elective initial coronary artery bypass graft (CABG) surgery. Right atrial appendage and skeletal muscle samples were obtained for tissue magnesium level analysis before, during (at 60th minute) and 30 minutes after cardiopulmonary bypass (CPB) with simultaneous blood samples. Daily measurements of blood Mg levels and continuous monitoring for AF were performed for 7 postoperative days. Statistical analyses were performed using ANOVA, independent samples t and Chi-square tests. RESULTS: AF developed in 5 out of 20 patients during postoperative period (25%). Patients with or without AF did not differ in terms of tissue and blood magnesium levels during and early after CPB and during 7 days after the operation. Blood magnesium levels were significantly higher in the whole study population on postoperative days 3 through 7 (day 3 - 1.13±0.11 mmol/L; day 4-, 1.18±0.07 mmol/L; day 5-1.15±0.10 mmol/L; day 6-1.17±0.08 mmol/L; and day 7, 1.22±0.08 mmol/L) compared to day 1 and day 2 (day 1-0.96±0.13 mmol/L and day 2-1.02±0.12 mmol/L; p=0.002 for all comparisons). CONCLUSION: Although patients with and without AF did not significantly differ with regard to blood and tissue magnesium levels, the coincidence of an early postoperative reduction in magnesium levels in all patients and occurrence of all AF incidences at this time period suggests a potential association deserving further investigation.

Octreotide in liver cirrhosis: a salvage for variceal bleeding can be a gunshot for kidneys.

BACKGROUND: The renal effects of octreotide, used for bleeding esophageal varices in cirrhosis, are controversial. METHODS: Fourteen cirrhotic patients (Child-Pugh; A/B/C: 1/12/1) were enrolled. Plasma nitrite and endothelin (ET) levels, urinary nitrite output, free water clearance (FWC) and fractional excretion of filtered sodium (FENa) were measured and renal Doppler ultrasound was carried out. Octreotide was infused at a rate of 0.75 microg/kg/h for 3 h after a bolus of 0.75 microg/kg body weight. All the parameters were reevaluated during octreotide administration while the patients acted as their own controls. RESULTS: Octreotide induced significant reductions in urinary nitrite, FENa and FWC. Plasma ET levels increased (baseline: 6.7 pg/ml, octreotide: 8.4 pg/ml), whereas the plasma nitrite level did not change significantly after octreotide infusion. Overall, no significant change in renal resistive index (RRI) could be demonstrated on Doppler after octreotide administration. However, patients with elevated baseline RRI values had significantly more deterioration in FWC and FENa compared with patients with normal RRI in response to octreotide. CONCLUSION: A marked decrease in FENa, FWC and urinary nitrite output, together with a significant increase in plasma ET level in response to octreotide, may indicate renal dysfunction in cirrhotic patients. This deleterious renal effect of octreotide may be more enhanced in patients with elevated baseline RRI.

Endothelin receptor blockers reduce I/R-induced intestinal mucosal injury: role of blood flow.

The aim of the present study was to assess the role of endothelin (ET) in ischemia-reperfusion (I/R)-induced mucosal injury. Mucosal permeability ((51)Cr-EDTA clearance) and tissue myeloperoxidase (MPO) activity were significantly increased after 30 min of ischemia followed by 30 min of reperfusion. The I/R-induced increases in mucosal permeability and polymorphonuclear leukocyte (PMN) infiltration were significantly attenuated by pretreatments with ET(A) (BQ-485) and/or ET(B) (BQ-788) receptor antagonists. Monoclonal antibody (MAb) directed against intercellular adhesion molecule-1 (ICAM-1; MAb 1A29) and superoxide dismutase (SOD) pretreatments significantly attenuated the increased mucosal permeability and PMN infiltration in a similar manner as with ET receptor antagonists. Superior mesenteric artery blood flow was significantly reduced during the reperfusion period. Both ET receptor antagonists caused a significant rise in blood flow compared with an untreated I/R group. In conclusion, our data suggest that ET(A) and/or ET(B) receptors, ICAM-1, and superoxide play an important role in I/R-induced mucosal dysfunction and PMN infiltration. Furthermore, ET is involved in the pathogenesis of post-reperfusion-induced damage and beneficial effects of ET receptor antagonism are related to an improvement of disturbed blood flow during the reperfusion period.