scholarly journals In vivo targeting of inducible NO synthase with oligodeoxynucleotides protects rat kidney against ischemia.

1996 ◽  
Vol 97 (10) ◽  
pp. 2377-2383 ◽  
Author(s):  
E Noiri ◽  
T Peresleni ◽  
F Miller ◽  
M S Goligorsky
Keyword(s):  
Rat Kidney ◽  
No Synthase ◽  
Inducible No Synthase

scholarly journals Sevoflurane Promotes Bactericidal Properties of Macrophages through Enhanced Inducible Nitric Oxide Synthase Expression in Male Mice

2019 ◽  
Vol 131 (6) ◽  
pp. 1301-1315 ◽  
Author(s):  
Thomas J. Gerber ◽  
Valérie C. O. Fehr ◽  
Suellen D. S. Oliveira ◽  
Guochang Hu ◽  
Randal Dull ◽  
...  
Keyword(s):  
Early Stage ◽  
No Synthase ◽  
Control Group ◽  
Male Mice ◽  
Proinflammatory Response ◽  
E Coli ◽  
Inducible No Synthase ◽  
Bactericidal Properties

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Sevoflurane with its antiinflammatory properties has shown to decrease mortality in animal models of sepsis. However, the underlying mechanism of its beneficial effect in this inflammatory scenario remains poorly understood. Macrophages play an important role in the early stage of sepsis as they are tasked with eliminating invading microbes and also attracting other immune cells by the release of proinflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α. Thus, the authors hypothesized that sevoflurane mitigates the proinflammatory response of macrophages, while maintaining their bactericidal properties. Methods Murine bone marrow–derived macrophages were stimulated in vitro with lipopolysaccharide in the presence and absence of 2% sevoflurane. Expression of cytokines and inducible NO synthase as well as uptake of fluorescently labeled Escherichia coli (E. coli) were measured. The in vivo endotoxemia model consisted of an intraperitoneal lipopolysaccharide injection after anesthesia with either ketamine and xylazine or 4% sevoflurane. Male mice (n = 6 per group) were observed for a total of 20 h. During the last 30 min fluorescently labeled E. coli were intraperitoneally injected. Peritoneal cells were extracted by peritoneal lavage and inducible NO synthase expression as well as E. coli uptake by peritoneal macrophages was determined using flow cytometry. Results In vitro, sevoflurane enhanced lipopolysaccharide-induced inducible NO synthase expression after 8 h by 466% and increased macrophage uptake of fluorescently labeled E. coli by 70% compared with vehicle-treated controls. Inhibiting inducible NO synthase expression pharmacologically abolished this increase in bacteria uptake. In vivo, inducible NO synthase expression was increased by 669% and phagocytosis of E. coli by 49% compared with the control group. Conclusions Sevoflurane enhances phagocytosis of bacteria by lipopolysaccharide-challenged macrophages in vitro and in vivo via an inducible NO synthase–dependent mechanism. Thus, sevoflurane potentiates bactericidal and antiinflammatory host-defense mechanisms in endotoxemia.

scholarly journals Selective Inhibition of Inducible NO Synthase Activity In Vivo Reverses Inflammatory Abnormalities in Surfactant Protein D-Deficient Mice

2007 ◽  
Vol 179 (12) ◽  
pp. 8090-8097 ◽  
Author(s):  
Elena N. Atochina-Vasserman ◽  
Michael F. Beers ◽  
Helchem Kadire ◽  
Yaniv Tomer ◽  
Adam Inch ◽  
...  
Keyword(s):  
Selective Inhibition ◽  
Surfactant Protein ◽  
No Synthase ◽  
Surfactant Protein D ◽  
Inducible No Synthase ◽  
Deficient Mice

Mechanisms of endotoxin-induced dilatation of cerebral arterioles

1995 ◽  
Vol 269 (3) ◽  
pp. H783-H788 ◽  
Author(s):  
J. E. Brian ◽  
D. D. Heistad ◽  
F. M. Faraci
Keyword(s):  
No Synthase ◽  
Vascular Responses ◽  
Time Points ◽  
Cranial Window ◽  
Inducible No Synthase ◽  
Calcitonin Gene ◽  
Cerebral Arterioles ◽  
Arteriolar Diameter ◽  
Inducible Nitric Oxide

Lipopolysaccharide (LPS; endotoxin) produces dilatation of cerebral arterioles in vivo which may be due, in part, to expression of inducible nitric oxide (NO) synthase. We tested the hypothesis that aminoguanidine, an inhibitor of inducible NO synthase, would reduce endotoxin-induced dilatation of cerebral arterioles. Because mechanisms other than expression of inducible NO synthase may contribute to endotoxin-induced dilatation of cerebral arterioles, we also tested the hypothesis that calcitonin gene-related peptide (CGRP) contributes to vascular responses to endotoxin. Cerebral arteriolar diameter was measured using a closed cranial window in anesthetized rabbits under control conditions [77 +/- 3 (SE) microns] and during topical application of endotoxin (100 micrograms/ml). After 4 h, diameter of cerebral arterioles increased by 41 +/- 5%. Coapplication of aminoguanidine (0.3 mM) with endotoxin reduced vasodilatation at all time points (30 min to 4 h). Relative to control values, endotoxin treatment increased guanosine 3',5'-cyclic monophosphate (cGMP) concentration in cerebrospinal fluid (CSF) by approximately 20 fold at 4 h. Aminoguanidine attenuated the endotoxin-induced increased in CSF cGMP concentration. Aminoguanidine (0.3 mM) did not alter acetylcholine-mediated dilatation of cerebral arterioles. Coapplication of CGRP-(8-37) (0.5 microM), a specific blocker of CGRP receptors, with endotoxin significantly reduced vasodilatation in response to endotoxin at 2, 3, and 4 h. Thus 1) aminoguanidine inhibits endotoxin- but not acetylcholine-mediated dilatation of cerebral arterioles, and 2) activation of CGRP receptors mediates a portion of endotoxin-induced dilation of cerebral arterioles.

Inhaled nitric oxide does not alter endotoxin-induced nitric oxide synthase activity during rat lung perfusion

1995 ◽  
Vol 79 (4) ◽  
pp. 1088-1092 ◽  
Author(s):  
M. M. Kurrek ◽  
L. Castillo ◽  
K. D. Bloch ◽  
S. R. Tannenbaum ◽  
W. M. Zapol
Keyword(s):  
Nitric Oxide ◽  
Feedback Inhibition ◽  
Ex Vivo ◽  
Lung Perfusion ◽  
No Synthase ◽  
Rat Lung ◽  
Ex Vivo Lung Perfusion ◽  
Inducible No Synthase ◽  
Isolated Lung

Nitric oxide (NO) has been demonstrated to decrease its own synthesis in tissue preparations. We tested the hypothesis that endogenous NO synthesis induced by lipopolysaccharides (LPS) would be decreased by exogenous NO during isolated lung perfusion. Rats were pretreated with either saline or LPS 48 h before lung harvest. Endogenous NO synthase activity was measured as conversion of L-[14C]-arginine to L-[14C]citrulline during 90 min of perfusion. NO (100 ppm) was added to the ventilating gas during perfusion of lungs from one group of control or LPS-treated rats. A second group of control or LPS-treated rats was exposed chronically to 100 ppm NO for the 48 h before lung harvest, in addition to receiving 100 ppm NO added to the ventilating gas during lung perfusion. We conclude that conversion of L-[14C]arginine to L-[14C]citrulline was minimal in control lungs and increased in response to LPS pretreatment. NO added to the ventilating gas for the 90 min of ex vivo perfusion did not alter the rate of L-[14C]citrulline production. In vivo exposure to 100 ppm NO for 48 h did not alter the induction of inducible NO synthase activity as measured during ex vivo lung perfusion. This indicates that inhaled NO does not exert negative-feedback inhibition on inducible NO synthase in the ex vivo rat lung.

scholarly journals Nitric Oxide Measurements during Endotoxemia

2001 ◽  
Vol 47 (6) ◽  
pp. 1068-1074 ◽  
Author(s):  
Viktor Brovkovych ◽  
Lawrence W Dobrucki ◽  
Svitlana Brovkovych ◽  
Iwona Dobrucki ◽  
Leszek Kalinowski ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Total Concentration ◽  
Pulmonary Arteries ◽  
No Synthase ◽  
No Production ◽  
Subsequent Increase ◽  
Pathological Conditions ◽  
Inducible No Synthase

Abstract Background: Excessive continuous NO release from inducible NO synthase over prolonged periods under pathological conditions, such as endotoxemia, contributes significantly to circulatory failure, hypotension, and septic shock. This NO production during endotoxemia is accompanied by superoxide release, which contributes to the fast decay of NO. Therefore, the amount of NO that diffuses to target sites may be much lower than the total amount released under pathological conditions. Methods: We performed in vivo and ex vivo measurements of NO (electrochemical) and ex vivo in situ measurements of superoxide, peroxynitrite (chemiluminescence), and nitrite and nitrate (ultraviolet-visible spectroscopy). We determined the effect of lipopolysaccharide administration (20 mg/kg) on diffusible NO, total NO (diffusible plus consumed in chemical reactions), and superoxide and peroxynitrite release in the pulmonary arteries of rats. Results: An increase in diffusible NO generated by constitutive NO synthase was observed immediately after administration of lipopolysaccharide, reaching a plateau (145 ± 18 nmol/L) after 540 ± 25 s. The plateau was followed by a decrease in NO concentration and its subsequent gradual increase after 45 min because of NO production by inducible NO synthase. The concentration of superoxide increased from 16 ± 2 nmol/L to 30 ± 3 nmol/L after 1 h and reached a plateau of 41 ± 4 nmol/L after 6 h. In contrast to the periodic changes in the concentration of diffusible NO, the total concentration of NO measured as a sum of nitrite and nitrate increased steadily during the entire period of endotoxemia, from 2.8 ± 0.2 μmol/L to 10 ± 1.8 μmol/L. Conclusions: The direct measurement of NO concentrations in the rat pulmonary artery demonstrates dynamic changes throughout endotoxemia, which are related to the production of superoxide and the subsequent increase in peroxynitrite. Monitoring endotoxemia with total nitrate plus nitrite is not sensitive to these fluctuations in NO concentration.

scholarly journals In vivo regulation of inducible NO synthase in immune-mediated liver injury in mice

Hepatology ◽  
2002 ◽  
Vol 36 (5) ◽  
pp. 1061-1069 ◽  
Author(s):  
Kerstin Koerber ◽  
Gabriele Sass ◽  
Alexandra K. Kiemer ◽  
Angelika M. Vollmar ◽  
Gisa Tiegs
Keyword(s):  
Liver Injury ◽  
No Synthase ◽  
Inducible No Synthase ◽  
Immune Mediated

Interleukin-1β inhibits rat thyroid cell function in vivo and in vitro by an NO-independent mechanism and induces hypothyroidism and accelerated thyroiditis in diabetes-prone BB rats

1996 ◽  
Vol 151 (1) ◽  
pp. 147-157 ◽  
Author(s):  
J I Reimers ◽  
A K Rasmussen ◽  
A E Karlsen ◽  
U Bjerre ◽  
H Liang ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
No Synthase ◽  
Interleukin 1Β ◽  
Iodine Uptake ◽  
Thyroid Cell ◽  
Bb Rats ◽  
Inducible No Synthase ◽  
Rat Thyroid

Abstract Interleukin-1β has been implicated as a pathogenic factor in the development of autoimmune thyroiditis. When given for 5 days to normal non-diabetes-prone Wistar Kyoto rats, it decreased plasma concentrations of total tri-iodothyronine and thyroxine and increased plasma TSH. These effects were not prevented by co-injection of nitroarginine methyl ester or aminoguanidine, inhibitors of NO synthases. Exposure to interleukin-1β dose-dependently reduced iodine uptake in FRTL-5 cells, but had no effect on thyroglobulin secretion. Nitrite was not detected in the FRTL-5 cell culture media after exposure to interleukin-1β. However, reverse transcription PCR analysis of mRNA isolated from interleukin-1β-exposed FRTL-5 cells revealed a transitory expression of the inducible NO synthase, which was markedly lower than inducible NO synthase induction in interleukin-1β-exposed isolated rat islets of Langerhans. Co-incubation with the NO synthase inhibitor NG-monomethylarginine did not ameliorate the effect of interleukin-1β on FRTL-5 cell iodine uptake. Furthermore, we demonstrate that daily injections of interleukin-1β for 13 weeks aggravated spontaneous thyroiditis and induced severe hypothyroidism in non-diabetic diabetes-prone BB rats. The data suggest that NO does not mediate interleukin-1β-induced inhibition of rat thyroid function in vivo or in vitro in FRTL-5 cells, and the induction of hypothyroidism by interleukin-1β in diabetes-prone BB rats is speculated to be due to exacerbation of recruitment and activation of intrathyroidal mononuclear cells. Journal of Endocrinology (1996) 151, 147–157

In vivo regulation of endothelium-dependent vasodilation in the rat renal circulation and the effect of streptozotocin-induced diabetes

2008 ◽  
Vol 295 (3) ◽  
pp. R829-R839 ◽  
Author(s):  
Amanda J. Edgley ◽  
Marianne Tare ◽  
Roger G. Evans ◽  
Con Skordilis ◽  
Helena C. Parkington
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Rat Kidney ◽  
Area Under The Curve ◽  
No Synthase ◽  
Renal Circulation ◽  
Prostanoid Production ◽  
Streptozotocin Induced Diabetes ◽  
Stimulation Of

We assessed the relative contributions of endothelium-derived relaxing factors to renal vasodilation in vivo and determined whether these are altered in established streptozotocin-induced diabetes. In nondiabetic rats, stimulation of the endothelium by locally administered ACh or bradykinin-induced transient renal hyperemia. Neither basal renal blood flow (RBF) nor renal hyperemic responses to ACh or bradykinin were altered by blockade of prostanoid production (indomethacin) or by administration of charybdotoxin (ChTx) plus apamin to block endothelium-derived hyperpolarizing factor (EDHF). In contrast, combined blockade of nitric oxide (NO) synthase, Nω-nitro-l-arginine methyl ester (l-NAME), and prostanoid production reduced basal RBF and the duration of the hyperemic responses to ACh and bradykinin and revealed a delayed ischemic response to ACh. Accordingly, l-NAME and indomethacin markedly reduced integrated (area under the curve) hyperemic responses to ACh and bradykinin. Peak increases in RBF in response to ACh and bradykinin were not reduced by l-NAME and indomethacin but were reduced by subsequent blockade of EDHF. l-NAME plus indomethacin and ChTx plus apamin altered RBF responses to endothelium stimulation in a qualitatively similar fashion in diabetic and nondiabetic rats. The integrated renal hyperemic responses to ACh and bradykinin were blunted in diabetes, due to a diminished contribution of the component abolished by l-NAME plus indomethacin. We conclude that NO dominates integrated hyperemic responses to ACh and bradykinin in the rat kidney in vivo. After prior inhibition of NO synthase, EDHF mediates transient renal vasodilation in vivo. Renal endothelium-dependent vasodilation is diminished in diabetes due to impaired NO function.

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