[P3-187]: EFFECTS OF EXERCISE ON PLASMA NITRITE/NITRATE LEVELS, AND NITRIC OXIDE SYNTHASE ACTIVITY IN ELDERLY AFRICAN AMERICANS WITH MILD COGNITIVE IMPAIRMENT

Background Recent evidence suggests that nitric oxide produced via the neuronal nitric oxide synthase is involved mainly in the early response to sepsis, whereas nitric oxide derived from the inducible nitric oxide synthase is responsible during the later phase. We hypothesized that early neuronal and delayed inducible nitric oxide synthase blockade attenuates multiple organ dysfunctions during sepsis. Methods Sheep were randomly allocated to sham-injured, nontreated animals (n = 6); injured (48 breaths of cotton smoke and instillation of Pseudomonas aeruginosa into the lungs), nontreated animals (n = 7); and injured animals treated with a neuronal nitric oxide synthase inhibitor from 1 to 12 h and an inducible nitric oxide synthase inhibitor from 12 to 24 h postinjury (n = 6). Results The injury induced arterial hypotension, vascular leakage, myocardial depression, and signs of renal and hepatic dysfunctions. The treatment significantly attenuated, but did not fully prevent, the decreases in mean arterial pressure and left ventricular stroke work index. Although the elevation of creatinine levels was partially prevented, the decreases in urine output and creatinine clearance were not affected. The injury-related increases in bilirubin levels, international normalized ratio, and lipid peroxidation in liver tissue were significantly attenuated. Although plasma nitrite/nitrate levels were significantly increased versus baseline from 12-24 h in controls, plasma nitrite/nitrate levels were not increased in treated animals. Conclusions The combination treatment shows potential benefit on sepsis-related arterial hypotension and surrogate parameters of organ dysfunctions in sheep. It may be crucial to identify the time course of expression and activation of different nitric oxide synthase isoforms in future investigations.

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Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals

Free Radical Biology and Medicine ◽

10.1016/s0891-5849(03)00406-4 ◽

2003 ◽

Vol 35 (7) ◽

pp. 790-796 ◽

Cited By ~ 412

Author(s):

Petra Kleinbongard ◽

André Dejam ◽

Thomas Lauer ◽

Tienush Rassaf ◽

Achim Schindler ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Plasma Nitrite ◽

Constitutive Nitric Oxide Synthase ◽

Oxide Synthase ◽

Nitric Oxide Synthase Activity

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Analysis of nitrite, nitrate, and nitric oxide synthase activity in brain tissue by automated flow injection technique

Methods in Enzymology - Nitric Oxide Part A: Sources and Detection of NO; NO Synthase ◽

10.1016/s0076-6879(96)68017-3 ◽

1996 ◽

pp. 152-159 ◽

Cited By ~ 10

Author(s):

Isao Yokoi ◽

Hitoshi Habu ◽

Hideaki Kabuto ◽

Akitane Mori

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Brain Tissue ◽

Flow Injection ◽

Injection Technique ◽

Nitrite Nitrate ◽

Oxide Synthase ◽

Nitric Oxide Synthase Activity

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Comparison of Effects of Nitric Oxide Synthase (NOS) Inhibitors on Plasma Nitrite/Nitrate Levels and Tissue NOS Activity in Septic Organs

Microbiology and Immunology ◽

10.1111/j.1348-0421.2005.tb03713.x ◽

2005 ◽

Vol 49 (2) ◽

pp. 139-147 ◽

Cited By ~ 26

Author(s):

Yuri Hayashi ◽

Masayoshi Abe ◽

Akira Murai ◽

Naomi Shimizu ◽

Iku Okamoto ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Nos Inhibitors ◽

Nitrite Nitrate ◽

Plasma Nitrite ◽

Oxide Synthase

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Effects of inhibition of nitric oxide synthase by aminoguanidine in acute endotoxemia

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.272.2.h843 ◽

1997 ◽

Vol 272 (2) ◽

pp. H843-H850 ◽

Cited By ~ 3

Author(s):

C. E. Hock ◽

K. Yin ◽

G. Yue ◽

P. Y. Wong

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Salmonella Enteritidis ◽

Fold Increase ◽

Myeloperoxidase Activity ◽

Cardiac Depression ◽

Arterial Blood ◽

Nitrite Nitrate ◽

Plasma Nitrite ◽

Oxide Synthase

Nitric oxide (NO) has been implicated in the pathogenesis of the circulatory dysfunction of endotoxin shock. We investigated the effect of aminoguanidine (AG), an inhibitor of nitric oxide synthase (NOS) that is more selective for the inducible NOS, on the circulatory and inflammatory sequelae after administration of a bolus (10 mg/kg iv) of lipopolysaccharide (LPS) (Salmonella enteritidis). Rats receiving LPS + vehicle (LPS + Veh) exhibited a 73% decrease in mean arterial blood pressure (MABP) and a 50% decrease in cardiac index (CI) and SV index (SVI) within 10 min after LPS administration. MABP recovered to 64 +/- 3, 81 +/- 6, and 79 +/- 8 mmHg, at 60, 120, and 180 min post-LPS, respectively. However, CI and SVI remained depressed by 40-50% for the entire experimental period. Systemic vascular resistance (SVRI), heart rate (HR), and hematocrit were significantly elevated at 180 min after LPS administration. There was a 15-fold increase in plasma nitrite/nitrate and significantly elevated tissue nitrite/nitrate in the lung, heart, liver, and intestine after 3 h of acute endotoxemia. Treatment with AG markedly decreased plasma nitrite/nitrate but did not alter the initial hypotension or cardiac depression. However, at 60 min after LPS administration the HR, MABP, and SVRI were higher in the AG-treated rats compared with vehicle, whereas CI and SVI remained depressed. Myeloperoxidase activity was significantly increased in the lung but not in the other tissues after LPS. The AG infusion significantly reduced tissue nitrite/nitrate in the lung and heart compared with LPS + Veh. The data suggest that neither NO nor acute inflammatory cell accumulation is solely responsible for the depressed cardiovascular function after intravenous administration of LPS.

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Propofol Attenuates Diaphragmatic Dysfunction Induced by Septic Peritonitis in Hamsters

Anesthesiology ◽

10.1097/00000542-200104000-00020 ◽

2001 ◽

Vol 94 (4) ◽

pp. 652-660 ◽

Cited By ~ 18

Author(s):

Katsuya Mikawa ◽

Kahoru Nishina ◽

Shun-ichi Kodama ◽

Hidefumi Obara

Keyword(s):

Nitric Oxide ◽

Inducible Nitric Oxide Synthase ◽

Endurance Capacity ◽

Diaphragmatic Dysfunction ◽

Septic Peritonitis ◽

Nitrite Nitrate ◽

Plasma Nitrite ◽

Oxide Synthase ◽

Nitric Oxide Synthase Activity ◽

Inducible Nitric Oxide

Background Sepsis or peritonitis impairs diaphragmatic contractility and endurance capacity. Peroxynitrite, a powerful oxidant formed by superoxide and nitric oxide, has been implicated in the pathogenesis. Propofol scavenges this reactive molecule. The authors conducted the current study to evaluate whether propofol prevents diaphragmatic dysfunction induced by septic peritonitis. Methods Forty male Golden-Syrian hamsters (120-140 g) were randomly classified into five groups. Groups sham and sham-propofol 50 underwent sham laparotomy alone, whereas groups sepsis, sepsis-propofol 25, and sepsis-propofol 50 underwent cecal ligation with puncture. Groups sham and sepsis received infusion of intralipid, whereas groups sham-propofol 50, sepsis-propofol 25, and sepsis-propofol 50 received propofol at rates of 50, 25, and 50 mg.kg(-1).h(-1), respectively. Intralipid or propofol was subcutaneously infused from 3 h before surgery until 24 h after operation, when all hamsters were killed. Diaphragmatic contractility and fatigability were assessed in vitro using diaphragm muscle strips. Peroxynitrite formation in the diaphragm was assessed by nitrotyrosine immunostaining. Plasma nitrite-nitrate concentrations and diaphragmatic concentrations of malondialdehyde were determined. Using another set of animals, diaphragmatic inducible nitric oxide synthase activity was also measured. Results Twitch, tetanic tensions, and tensions during fatigue trials were reduced in group sepsis compared with group sham. In group SEPSIS, diaphragm malondialdehyde and inducible nitric oxide synthase activity, and plasma nitrite-nitrate concentrations increased, and positive immunostaining for nitrotyrosine residues was found. Propofol attenuated these changes. Conclusions Pretreatment with propofol attenuated diaphragmatic dysfunction induced by septic peritonitis in hamsters assessed by contractile profiles and endurance capacity. This beneficial effect of propofol may be caused, in part, by inhibition of lipid peroxidation in the diaphragm caused by the powerful oxidant.

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Effects of oral L-NAME during Trichinella spiralis infection in rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1996.271.2.g338 ◽

1996 ◽

Vol 271 (2) ◽

pp. G338-G346 ◽

Cited By ~ 6

Author(s):

C. M. Hogaboam ◽

S. M. Collins ◽

M. G. Blennerhassett

Keyword(s):

Nitric Oxide ◽

Smooth Muscle ◽

Nitric Oxide Synthase ◽

Trichinella Spiralis ◽

Intestinal Smooth Muscle ◽

Inos Mrna ◽

Cell Hyperplasia ◽

Plasma Nitrite ◽

Oxide Synthase ◽

Nitric Oxide Synthase Activity

We investigated the involvement of nitric oxide in transmural jejunal alterations induced by Trichinella spiralis (T. spiralis) infection in rats. Rats were gavaged with either saline or T.spiralis larvae, and, 1 h later, rats were treated orally with water, NG-nitro-L-arginine methyl ester (L-NAME; 30 mg/kg), or NG-nitro-D-arginine methyl ester (D-NAME; 30 mg/kg) on a daily basis. Although not observed in jejunum from uninfected rats, inducible nitric oxide synthase (iNOS) mRNA was present in the mucosa and neuromuscular layers of jejunum from T. spiralis-infected rats. On day 6, T. spiralis-infected rats had a 6-fold decrease in transmural nitric oxide synthase activity, an 11-fold increase in plasma nitrite, and a 7-fold elevation in transmural myeloperoxidase (MPO) activity compared with uninfected controls. Intestinal smooth muscle cell hyperplasia and hypertrophy were only detected in the infected rats. L-NAME, but not D-NAME, treatment of infected rats for 6 days caused a pronounced increase in transmural iNOS mRNA expression, coinciding with significantly increased mucosal nitric oxide synthase activity. T. spiralis numbers in L-NAME-treated rats were significantly lower compared with the other two infected groups although L-NAME had no direct effect on T. spiralis viability in vitro. Furthermore, L-NAME treatment significantly reduced plasma nitrite and jejunal MPO but not intestinal smooth muscle cell hyperplasia or hypertrophy. In contrast, D-NAME treatment of infected rats significantly enhanced intestinal smooth muscle hyperplasia and hypertrophy. Taken together, these results suggest that alterations in the T. spiralis-infected jejunum are mediated, in part, by a suppression of nitric oxide synthase activity in the inflamed jejunum.

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