Formation of Free Radicals and Nitric Oxide Derivative of Hemoglobin in Rats During Shock Syndrome

Westenberger, Ulrich; Thanner, Siegfried; Ruf, Hans Heinrich; Gersonde, Klaus; Sutter, Günter; Trentz, O.

doi:10.3109/10715769009109680

Cited by 134 publications

(53 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have already shown that LPS and NO donor treatment increase the HbNO concentration in blood, and clear HbNO spectra have been successfully obtained using the EPR method without any modifications (10,28,31,67,69). However, we and others failed to detect the distinct EPR signal of HbNO in the blood of normal humans or animals.…”

Section: Discussioncontrasting

confidence: 45%

See 1 more Smart Citation

Evaluation of systemic blood NO dynamics by EPR spectroscopy: HbNO as an endogenous index of NO

Kirima¹,

Tsuchiya²,

Séi³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

.-The measurement of hemoglobin-nitric oxide (NO) adduct (HbNO) in whole blood by the electron paramagnetic resonance (EPR) method seems relevant for the assessment of systemic NO levels. However, ceruloplasmin and unknown radical species overlap the same magnetic field as that of HbNO. To reveal the EPR spectrum of HbNO, we then introduced the EPR signal subtraction method, which is based on the computer-assisted subtraction of the digitized EPR spectrum of HbNO-depleted blood from that of sample blood using the software. Rats were treated with N -nitro-Larginine methyl ester (L-NAME; 120 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ) for 1 wk to obtain HbNO-depleted blood. When this method was applied to the analysis of untreated fresh whole blood, the five-coordinate state of HbNO was observed. HbNO concentration in pentobarbital-anesthetized rats was augmented (change in [HbNO] ϭ 1.6-5.5 M) by infusion of L-arginine (0.2-0.6 g/kg) but not D-arginine. Using this method, we attempted to evaluate the effects of temocapril on HbNO dynamics in an L-NAME-induced rat endothelial dysfunction model. The oral administration of L-NAME for 2 wk induced a serious hypertension, and the HbNO concentration was reduced (change in [HbNO] ϭ 5.7 M). Coadministration of temocapril dose dependently improved both changes in blood pressure and the systemic HbNO concentration. In this study, we succeeded in measuring the blood HbNO level as an index of NO by the EPR HbNO signal subtraction method. We also demonstrated that temocapril improves abnormalities of NO dynamics in L-NAME-induced endothelial dysfunction rats using the EPR HbNO signal subtraction method. nitric oxide; hemoglobin-nitric oxide adduct; electron paramagnetic resonance; temocapril NITRIC OXIDE (NO), a free radical molecule, has numerous roles in various physiological functions, such as the regulation of the cardiovascular, immune, and nervous systems. An imbalance of NO results in many diseases such as hypertension, atherosclerosis, septic and hemorrhage shock, ischemia-reperfusion injury, diabetes, and neurodegenerative disorders (18, 40,70).Because of increasing interest in the effect of NO, an accurate method is required for the measurement of this radical. Several methods for the quantitation of NO such as chemiluminescence (46), methemoglobin formation (23), and electron paramagnetic resonance (EPR) spectroscopy of nitrosyl-metal complexes (15) have been developed (3). The Griess and cGMP methods have been widely used to measure NO production in vivo (35, 62) and in vitro (34, 61), but these values do not always reflect the concentration of NO, because of their poor specificities for blood NO. EPR spectroscopy is a technique used for the detection and measurement of free radical species. EPR methods using endogenous and exogenous spin-trapping agents, which stabilize NO as a polyatomic spin adduct, have been developed (1,4,29, 41,72).In the circulation, NO exists as relatively stable hemoglobin (Hb)-NO adduct (HbNO) (48), which means that the amount of HbNO may reflect the blood NO ...

show abstract

Section: Discussioncontrasting

confidence: 45%

“…Hb is known to bind to NO, resulting in the formation of HbNO, which has a characteristic EPR spectrum, and hence is used as a spin-trapping agent for NO in lipopolysaccharide (LPS)-treated (67,69) and NO donor-administered (10,28) animals.…”

mentioning

confidence: 99%

Evaluation of systemic blood NO dynamics by EPR spectroscopy: HbNO as an endogenous index of NO

Kirima¹,

Tsuchiya²,

Séi³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…This observation questions either the contribution of peroxynitrite to tissue damage or the relationship between peroxynitrite and nitrotyrosine. The fact that recent evidence suggests that ortho-nitrotyrosine may be formed from a number of sources that do not necessarily involve peroxynitrite, e.g., the reaction between nitrite and hypochlorous acid (10,32), may go in some way to explain our findings.…”

Section: Discussionmentioning

confidence: 59%

Increased activity and expression of iNOS in human duodenal enterocytes from patients with celiac disease

Murray

Daniels

Coupland

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

The activity of nitric oxide synthase (NOS) was assayed in enterocytes isolated from human duodenal biopsies to determine its role in celiac disease. Patients were categorized into groups with irritable bowel syndrome, iron-deficiency anemia, B12/folate deficiency, and treated and untreated celiac disease. Enterocytes isolated from all groups showed 1400W-inhibitable Ca2+-independent NOS activity with a pH level and temperature optimum of 9.4 and 37°C, respectively. Western blotting showed that enterocytes expressed the inducible NOS protein and proteins with nitrated tyrosine residues, the latter being indicative of nitric oxide-driven peroxynitrite and/or free-radical damage. Endothelial NOS was seen only in the lamina propria. Patients with celiac disease had higher NOS activity than other patient groups. Treatment of the condition led to a fall in activity. Enzyme-linked immunosorbent assay demonstrated cGMP production by the enterocyte fraction, but cGMP levels did not correlate with NOS activity. These results suggest that inducible NOS is constitutively expressed in human duodenal enterocytes, is increased in patients with untreated celiac disease, and is partially corrected when such patients are treated. We found no evidence to support a role for nitric oxide in the formation of cGMP within the small intestine. Furthermore, we were unable to demonstrate a role for peroxynitrite/free radical damage in the pathophysiology of celiac disease.

show abstract

“…17 Endotoxin administration source of serum NO 0 2 /NO 0 3 . 45 in the lung; in other words, NO measured in the exhaled air 10. Sieber CC, Lopez-Talavera JC, Groszmann RJ.…”

mentioning

confidence: 99%

Exhaled nitric oxide and oxygenation abnormalities in hepatic cirrhosis

et al. 1997

View full text Add to dashboard Cite

Impaired arterial oxygenation, ranging from increased alImpaired arterial oxygenation, ranging from increased alveolar-arterial oxygen gradient (AaDo 2 ) to hypoxemia, is veolar-arterial oxygen gradient (AaDo 2 ) to hypoxemia, is comcommonly reported in patients with cirrhosis. 1 In the absence monly present in patients with cirrhosis. Nitric oxide (NO), of overt mechanical dysfunction of the lung, it has been through pulmonary vasodilatation, may play a major role in suggested that oxygenation abnormalities of cirrhotic pathe oxygen abnormalities of cirrhosis. Our aim was to study tients may be a consequence of ventilation/perfusion misthe relationship between NO production and O 2 abnormalities match and intrapulmonary shunting. 2-4 Intrapulmonary vasin 45 nonsmoking patients with cirrhosis and without major cular dilatations and artero-venous communications are cardiovascular and respiratory diseases. Intrapulmonary thought to be the pathological bases of the physiological shunting was detected by contrast-enhanced (CE) echocardimechanisms of oxygenation abnormalities. 5,6 ography. Lung volumes and diffusion, arterial blood gas analy-The vascular dilatations can result in severe hypoxemia, sis, serum NO 0 2 /NO 0 3 , NO output in the exhaled air, and which, at variance from that caused by intrapulmonary cardiac index by the echocardiographic method were detershunts, may respond normally to supplemental oxygen. mined in all patients. Twenty-seven (60%) patients had anIncreased circulation of a pulmonary vasodilator seems abnormally increased (ú15 mm Hg) AaDo 2 . The mean values to be the favored mechanism for intrapulmonary vascular of exhaled NO output and serum NO 0 2 /NO 0 3 were significantly dilatations in cirrhosis, and nitric oxide (NO) has recently higher in cirrhotic patients than in controls (252 { 117 vs.ascended to the top of the list of possible substances. 6,7 75.2 { 19 nL/min/m 2 , P õ .0001; and 47.5 { 29.4 vs. 32.9NO is a powerful local vasodilator of endothelial origin, { 10.1 mmol/L, P õ .02, respectively). In all patients, there which contributes to the normally low pulmonary vascular was a significant correlation between exhaled NO and AaDo 2 tone. 8 NO has been shown to play an important role in regulat-(r Å .78, P õ .0001). Twelve patients (26.6%) were found to ing the vasomotor tone in experimental cirrhosis. 9,10 It is now have CE-echocardiographic evidence of intrapulmonary possible to measure NO produced in the lung by measuring its shunting (positive CE-echo). Nine patients were considered concentration in exhaled air. 11,12 Recently, increased NO output to have hepatopulmonary syndrome (HPS) on the basis of an in exhaled air has been reported in patients with advanced AaDo 2 ú 15 mm Hg and positive CE-echo. These 9 patients cirrhosis, in whom exhaled NO was associated with systemic had a mean value of exhaled NO significantly higher than circulatory disturbances. 13 Exhaled NO was reported to be patients without HPS (331 { 73.2 vs. 223 { 118.4 nL/min/ raised almost threefold in t...

show abstract

Formation of Free Radicals and Nitric Oxide Derivative of Hemoglobin in Rats During Shock Syndrome

Cited by 134 publications

References 17 publications

Evaluation of systemic blood NO dynamics by EPR spectroscopy: HbNO as an endogenous index of NO

Evaluation of systemic blood NO dynamics by EPR spectroscopy: HbNO as an endogenous index of NO

Increased activity and expression of iNOS in human duodenal enterocytes from patients with celiac disease

Exhaled nitric oxide and oxygenation abnormalities in hepatic cirrhosis

Contact Info

Product

Resources

About