UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examined the production of nitric oxide (NO) in the renal cortex and medulla through the use of an in vivo microdialysis technique. Oxyhemoglobin (OxyHb) at a concentration of 3 mumol/L was perfused through the dialysis system to trap tissue NO. Methemoglobin (MetHb), which was formed by NO oxidation of OxyHb in the dialysate, was spectrophotometrically assayed at 401 nm. Because the oxidation of OxyHb to produce MetHb is stoichiometric with NO, the production of NO can be determined by the rate of MetHb formation. We found that NO concentration was significantly higher (P < .05) in the medulla (57.1 +/- 5.57 nmol/L, n = 10) than in the cortex (31.2 +/- 5.7 nmol/L, n = 9). The minimal detectable NO level of this assay is approximately 10 nmol/L. Intravenous infusion of L-arginine (3 mg/kg per minute) for 30 minutes produced a twofold to three fold increase in cortical and medullary NO; NG-nitro-L-arginine methyl ester (L-NAME) (10 micrograms/kg per minute) decreased NO by 33% in the renal cortex and by 46.5% in the renal medulla. We have also compared under the same conditions the degradation products of NO, nitrite, and nitrate in the renal cortex and medulla using in vivo microdialysis combined with microtiter plate colorimetry. Nitrite/nitrate concentration was significantly higher (P < .05) in the medulla (2.7 +/- 0.6 mumol/L, n = 4) than in the cortex (2.1 +/- 0.2 mumol/L, n = 4). Infusion of L-arginine increased cortical and medullary nitrite/nitrate by 65% and 39%, respectively. L-NAME reduced cortical and medullary nitrite/nitrate by 18% and 23%, respectively. The results indicate that the OxyHb-NO microdialysis trapping technique is a highly sensitive in situ method for detecting regional tissue NO concentration and changes in the NO synthase activity in the kidney. These studies have shown that NO concentration is higher in medullary tissue than in the cortex.
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PMID:Nitric oxide in renal cortex and medulla. An in vivo microdialysis study. 903 1

1. Nitric oxide (NO) has been suggested as a gastrointestinal neurotransmitter, mediating the gastric receptive relaxation and the relaxation in the peristaltic reflex. The aim of the present study was to measure nerve-induced NO formation in vivo in the gastrointestinal tract. 2. Formation of the nitric oxide oxidation products nitrite and nitrate during vagal nerve stimulation were measured in the anaesthetized rabbit. Microdialysis probes were inserted into the wall of the stomach and proximal colon, and nitrite and nitrate in dialysate measured by capillary electrophoresis. 3. During bilateral vagal nerve stimulation there was an increase in nitrite and nitrate formation at the level of the stomach and in nitrite formation at the level of the colon. This increase was inhibited by intravenous administration of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME 30 mg kg-1). Furthermore, L-NAME significantly increased nerve-induced gastric and colonic contractions, as well as spontaneous colonic contractions. 4. In summary, we present a new methodological procedure for quantification of small changes in nitric oxide formation in vivo. This study provides evidence that nitric oxide is released in the stomach and colonic wall during vagal nerve activity, at concentrations able to cause inhibition of smooth muscle contractions in vivo.
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PMID:Nerve-induced release of nitric oxide in the rabbit gastrointestinal tract as measured by in vivo microdialysis. 905 11

The involvement of nitric oxide (NO) in anxiety was investigated in rats, using the elevated plus maze test. Acute, but not chronic, systemic treatment with N omega-nitro-L-arginine methyl ester (L-NAME, 10 and 60 mg.kg-1), an inhibitor of NO synthase, increased the time spent by the rats in the open arms. Both the acute and chronic treatments with L-NAME inhibited NO synthase in endothelial cells and in the central nervous system, as shown by the increase in mean arterial pressure and decreased NO synthase activity in brain tissue. Chronic treatment with L-NAME also decreased the serum nitrate levels. The anxiolysis induced by acute L-NAME treatment is unlikely to be due to hypertension, since two-kidney one-clip hypertension in non-L-NAME-treated rats failed to significantly change exploratory behaviour in the elevated plus maze. These results indicate that acute inhibition of NO synthesis decreases anxiety in rats.
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PMID:Acute inhibition of nitric oxide synthesis induces anxiolysis in the plus maze test. 910 74

1. We have studied the participation of nitric oxide (NO) in an animal model of inflammation, the rat air pouch stimulated with zymosan. 2. Saline or zymosan was injected into 6-day rat air pouches at different time points and measurements were made of cell migration, levels of nitrite/nitrate (NO2/NO3-), prostaglandin E2 (PGE2), leukotriene B4 (L.TB4) and secretory phospholipase A2 (sPLA2) in exudates. Nitric oxide synthase (NOS) activity was determined in high speed supernatants from cells present in pouch exudates. Western blot analysis was also performed on these samples. 3. Zymosan injection induced a time-dependent increase in leukocyte infiltration, NO2/NO3- levels and cellular NOS activity that reached a peak by 8 h. Western blot analysis showed the same time course for induction of NOS protein. Colchicine administration to rats inhibited cellular infiltration and decreased the levels of NO metabolites and cellular NOS activity zymosan-injected air pouch at 8 h. NOS activity was present in polymorphonuclear leukocytes (PMNs) and monocytes, but not in the lymphocytes present in exudates. This enzyme is calcium-independent and needs NADPH for activity. PGE2 levels in exudates showed a time course inverse to that of NOS activity and NO metabolites, with maximum levels of PGE2 observed at 4 h after zymosan injection. 4. Administration of NG-nitro-L-arginine methyl ester (L-NAME) or aminoguanidine to rats significantly reduced cellular NOS activity, NO2/NO3- levels and chemiluminescence, whereas they were without effect on cell migration and degranulation, eicosanoid levels and sPLA2 activity. 5. Treatment of animals with dexamethasone inhibited cellular NOS activity, NO2/NO3- levels, chemiluminescence and the increase in the levels of PGE2 and LTB4, with only a weak effect on elastase release. 6. Administration of the selective cyclo-oxygenase-2 (COX-2) inhibitor NS398 to rats strongly reduced PGE2 levels in exudates without affecting NO metabolites or NOS activity at 4 h after zymosan injection. 7. Our data indicate that NOS is induced in the zymosan-stimulated rat air pouch model of inflammation. This enzyme is expressed in the cells migrating into the air pouch and caused an increased production of NO metabolites in exudates. The results also suggest the presence of an earlier phase in which eicosanoids play the main role, with participation of COX-2 activity, and a later phase mediated by NO. The endogenous release of NO does not modify prostaglandin biosynthesis in this in vivo model.
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PMID:Nitric oxide synthase and cyclo-oxygenase pathways in the inflammatory response induced by zymosan in the rat air pouch. 911 64

Nitric oxide (NO) is a regulator of leukocyte adhesion in the microcirculation. This study was designed to examine the effects of a NO synthase inhibitor on neutrophil adhesion in the peritoneum, lung, liver, and kidney in a rat peritonitis model using a fluorescence microscopic method. Sprague-Dawley rats were given normal saline (control) or N omega-nitro-L-arginine methyl ester (L-NAME) at dosages of 10 mg/kg (N10) or 100 mg/kg (N100) (n = 66) intraperitoneally. One hour after pretreatment fluorescein-labeled neutrophils were infused without bacterial challenge (0 hr). Other rats received an injection of 10(7) Escherichia coli into the peritoneal cavity 1 hr after pretreatment. Labeled neutrophils were infused 1 and 5 hr after bacterial challenge. Just 2 min after neutrophil injection, blood samples were obtained and the animals were killed. Five peritoneal samples (omentum, mesentery, parietal peritoneum, colon, and ileum), both lungs, the liver, and the right kidney were harvested for counting of labeled neutrophils under epifluorescent microscopy. Combined plasma nitrite/nitrate levels were determined. In another set of rats (n = 36), an arterial catheter was inserted after L-NAME treatment and bacterial challenge. At 0, 1, 5, and 12 hr after challenge, blood pressure, heart rate, and arterial blood gas data were measured. One hour after E. coli challenge, the number of neutrophils in the peritoneum was significantly lower in both L-NAME-treated groups than in the control group. In contrast, the number of labeled neutrophils in the lungs was significantly higher in the N100 group than in the control group. Neutrophil accumulation in the lungs and peritoneum at 0 and 5 hr and in the liver and kidney at 0, 1, and 5 hr did not differ among groups, nor did combined plasma nitrite/nitrate levels. L-NAME treatment had no influence on either hemodynamic or blood gas data. In conclusion, administration of L-NAME increases neutrophil adhesion in the lung, while decreasing that in the peritoneum. NO plays an important role in neutrophil adhesion at the inflammatory site, as well as in remote organs, during peritonitis. NO inhibition may be detrimental, due to neutrophil sequestration, in this peritonitis model.
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PMID:Nitric oxide inhibition decreases neutrophil adhesion at the inflammatory site, while increasing adhesion in remote organs in peritonitis. 912 99

The goals of this study were to determine whether long-term nitric oxide (NO) synthesis inhibition in dogs results in an increase in the sodium sensitivity of arterial pressure and whether changes in plasma renin activity or the plasma concentrations of arginine vasopressin (AVP) and aldosterone play an important role in this hypertension. Studies were conducted in a control group and groups that received NO inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) at 10 or 25 microg x kg(-1) x min(-1). Each group was challenged with normal, low, and high sodium intake for periods of 5 days each. Urinary nitrate + nitrite excretion (UNOx) more than doubled in the control group during high sodium intake. In both L-NAME groups, UNOx decreased significantly, there was a hypertensive shift in the relation between urinary sodium excretion and arterial pressure, and urinary sodium excretion remained normal even in the high-sodium intake period. L-NAME infusion did not change the sodium sensitivity of arterial pressure or plasma renin activity, plasma aldosterone, and plasma AVP. In conclusion, the data suggest that, in dogs, increases in NO synthesis are not necessary to excrete a chronic sodium load, and decreases in NO do not increase the sodium sensitivity of arterial pressure.
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PMID:Role of nitric oxide in the arterial pressure and renal adaptations to long-term changes in sodium intake. 914 16

Nitric oxide (NO) is a biologically active molecule known to be enzymatically synthesized from L-arginine in the presence of NO synthetase (NOS). In this study, we demonstrate a novel non-enzymatic pathway for NO synthesis involving hydrogen peroxide and D- or L-arginine. We employed two measures of NO generation. The first consists in the demonstration of the oxidative metabolites of NO (NO2 + NO3 = NOx) and the second is the confirmatory finding of chemiluminescence derived from NO. The results show that NOx increases in the incubation mixture containing hydrogen peroxide coupled with D-arginine, L-arginine, L-canavanine, and even the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). However, chemiluminescence was detected only from the reactions of hydrogen peroxide and D- or L-arginine and was diminished by the addition of carboxy-2-phenyl-4, 4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (PTIO), a specific scavenger of NO, confirming NO generation in the reaction.
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PMID:A novel nonenzymatic pathway for the generation of nitric oxide by the reaction of hydrogen peroxide and D- or L-arginine. 914 13

1. Within vessels, the formation of nitric oxide (NO) or prostaglandins is normally catalysed in the endothelium by constitutive isoforms of NO synthase (eNOS) and cyclo-oxygenase (COX-1), respectively. However, during inflammatory conditions, the underlying smooth muscle acquires the ability to release NO and prostaglandins after the expression of inducible isoforms of NOS (iNOS) and COX (COX-2). The co-induction of iNOS and COX-2 has been studied over 24 h in isolated vascular smooth muscle cells in vitro. However, due to the limitation of using cultured cells, the relationship between the activities of iNOS and COX over longer periods has not been addressed. Moreover, the relative contribution of the endothelium to the production of NO and prostaglandins under inflammatory conditions is not completely understood. 2. Here using an organ culture system, we have determined the profile of COX (6-keto prostaglandin F1 alpha (6-keto PGF1 alpha), PGE2, thromboxane B2 (TXB2) and NOS (nitrite and nitrate) metabolites released over a period of 10 days from segments of rat aorta. In each case, segments from the same animal were left untreated or treated with bacterial lipopolysaccharide (LPS; 10 micrograms ml-1) in order to induce iNOS and COX-2. Prostaglandins were measured by radioimmunoassay whilst nitrite and nitrate were measured, respectively, by Greiss reaction alone, or following a nitrate reductase step. The isoforms of NOS and COX responsible for metabolite release were characterized pharmacologically by use of inhibitors and at the molecular level by reverse transcription polymerase chain reaction with specific primers for iNOS, eNOS, COX-1 and COX-2. In separate experiments the role of the endothelium in the release of nitrite, nitrate and prostaglandins and in the expression of iNOS, eNOS, COX-1 and COX-2 was determined by comparing responses in endothelium denuded and endothelium-intact segments of rat aorta. 3. Under control culture conditions vessels released prostaglandins in the following rank order 6-keto PGF1 alpha = PGE2 > > TXB2. LPS increased the release of 6-keto PGF1 alpha and PGE2 but not of TXB2, an effect that was inhibited by the protein synthesis inhibitor cycloheximide (1 microM), the anti-inflammatory steroid dexamethason (1 microM), the nonsteroidal anti-inflammatory drug indomethacin (30 microM) and, where tested, the selective COX-2 inhibitor NS-398 (30 microM). Similarly, segments of rat aorta released detectable levels of nitrite and nitrate, which were reduced by NG-nitro-L-arginine methyl ester (L-NAME, 1 mM), which inhibits all isoforms of NOS, and by dexamethasone (1 microM), which inhibits the induction of iNOS. The proportion of nitrate to nitrite released over the 10 day period varied greatly from approximately 1:1 on days 5 to 8 to 5:1 on day 9. However, the sum of nitrite and nitrate (NOx) as well as PGE2 remained elevated over the whole 10 day period. The formation of 6-keto PGF1 alpha peaked on days 1 and 2. 4. In freshly prepared tissue, mRNAs for eNOS, COX-1, iNOS and COX-2 were detected. After 24 h in culture, there was an apparent increase in the level of mRNAs for iNOS and COX-2 but not for eNOS or COX-1, an effect that was further enhanced when LPS was included in the culture medium. The expressions of mRNA for eNOS, COX-1, iNOS or COX-2 were not greatly different in vessels with intact or disrupted endothelium. Similarly the release of NOx or PGE2 by vessels after the 1st or 9th day in culture were not significantly different from vessels prepared with or without endothelium. 5. Thus, COX-2 and iNOS are co-induced in intact vessels in culture, with the vascular smooth muscle being the main site of mediator generation. In contrast to data from isolated cells in culture (observed usually over 1 day), both COX and NOS activities in cultured blood vessels were elevated for at least 10 days. Also, unlike isolated cells in culture, the COX and NOS pathways were active independently; L-NAME had little effect on the activity of COX and indomethacin had little effect on the activity of NOS.
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PMID:Characterization of the induction of nitric oxide synthase and cyclo-oxygenase in rat aorta in organ culture. 914 96

Nitric oxide (NO) is a short-lived mediator, the synthesis of which is induced by various cytokines during inflammatory processes. Recently, it has been proposed that zymosan, a nonbacterial agent, causes inflammation by inducing the production of various cytokines and proinflammatory mediators. In the present study we investigated the role of NO in a nonseptic shock model induced by zymosan administration in the rat. Administration of zymosan (500 mg/kg, intraperitoneally) in the rat induced acute peritonitis, as assessed by a marked increase in the leukocytes count in the exudate, as well as by an increase in the exudate nitrate/nitrite concentration. Zymosan-treated rats developed a severe hypotension and showed signs of systemic illness, significant loss of body weight, and a high mortality rate (53% of animals died within 72 h). Elevated plasma levels of nitrite and nitrate were also observed in zymosan-treated rats compared with control rats (67 +/- 4 microM and 23 +/- 2 microM, respectively; p < .01). In ex vivo experiments, vascular reactivity was studied in thoracic aorta rings of zymosan-treated rats. The contractile responses to norepinephrine (100 nM) and endothelin-1 (5 nM) were significantly reduced. An impairment of the endothelial-dependent relaxation in response to acetylcholine was also observed. Pretreatment of zymosan-shocked rats with NG-nitro-L-arginine methyl ester (L-NAME) or NG-monomethyl-L-arginine (L-NMA), (10 mg/kg, subcutaneously, 15 min before zymosan) decreased mortality, prevented the development of peritonitis, improved ex vivo vascular reactivity, and significantly reduced hypotension. Our data suggest that overproduction of NO plays a role in the zymosan-induced peritonitis and cardiovascular derangements in the rats.
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PMID:Role of nitric oxide in a nonseptic shock model induced by zymosan in the rat. 916 70

1. To investigate the role of nitric oxide (NO) in diabetic nephropathy the effect of nitric oxide synthase (NOS) inhibition by NG-nitro-L-arginine methyl ester (L-NAME) was observed in a streptozotocin diabetic spontaneously hypertensive rat (SHR) model. 2. Two groups of SHR (n = 8) with streptozotocin-induced diabetes were studied. One group was given L-NAME 5 mg/kg bodyweight per day in the drinking water for 8 weeks while both groups received daily subcutaneous injections of Ultratard insulin. Creatinine clearance, urinary protein excretion, urinary nitrate concentration and systolic blood pressure were measured at fortnightly intervals. Rats were killed at 8 weeks and plasma angiotensin II (AngII) was measured by radioimmunoassay. 3. Renal function (endogenous creatinine clearance) remained stable in both groups. In the L-NAME group, however, there was a progressive increase in proteinuria that was highly significant at 6 weeks (22.1 +/- 2.9 compared with 6.5 +/- 0.7 mg/ 24 h per 100 g in control SHR diabetic rats P < 0.001). 4. Systolic blood pressure was significantly elevated in the L-NAME group throughout the study compared with the control group. 5. Plasma AngII was significantly elevated in the L-NAME group compared with controls (42.8 +/- 10.3 vs 15.1 +/- 1.9 pmol/L, respectively; P < 0.05). 6. Activation of the renin-angiotensin system may account, at least in part, for the resulting vasoconstrictor activity with chronic nitric oxide depletion.
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PMID:Nitric oxide synthase inhibition in a spontaneously hypertensive rat model of diabetic nephropathy. 917 57

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