NITRIC OXIDE INTERFERES WITH HYPOXIA SIGNALING DURING COLONIC INFLAMMATION

Context Intestinal inflammation can induce a local reduction in oxygen levels that triggers an adaptive response centered on the expression of hypoxia-inducible factors (HIFs). Nitric oxide, a well-described inflammatory mediator, may interfere with hypoxia signaling. Objectives We aimed to evaluate the role of nitric oxide in hypoxia signaling during colonic inflammation. Methods Colitis was induced by single (acute) or repeated (reactivated colitis) trinitrobenzenosulfonic acid administration in rats. In addition, one group of rats with reactivated colitis was also treated with Nw-Nitro-L-arginine methyl ester hydrochloride to block nitric oxide synthase. Colitis was assessed by macroscopic score and myeloperoxidase activity in the colon samples. Hypoxia was determined using the oxygen-dependent probe, pimonidazole. The expression of HIF-1α and HIF-induced factors (vascular endothelial growth factor - VEGF and apelin) was assessed using Western blotting. Results The single or repeated administration of trinitrobenzenosulfonic acid to rats induced colitis which was characterized by a high macroscopic score and myeloperoxidase activity. Hypoxia was observed with both protocols. During acute colitis, HIF-1α expression was not increased, but VEGF and apelin were increased. HIF-1α expression was inhibited during reactivated colitis, and VEGF and apelin were not increased. Nw-Nitro-L-arginine methyl ester hydrochloride blockade during reactivated colitis restored HIF-1α, VEGF and apelin expression. Conclusions Nitric oxide could interfere with hypoxia signaling during reactivated colitis inflammation modifying the expression of proteins regulated by HIF-1α.

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Nitric oxide and β-adrenergic agonist-induced bronchial arterial vasodilation

Journal of Applied Physiology ◽

10.1152/jappl.1997.82.2.686 ◽

1997 ◽

Vol 82 (2) ◽

pp. 686-692 ◽

Cited By ~ 14

Author(s):

Nirmal B. Charan ◽

Shane R. Johnson ◽

S. Lakshminarayan ◽

William H. Thompson ◽

Paula Carvalho

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Methyl Ester ◽

No Synthase ◽

Ester Hydrochloride ◽

Methyl Ester Hydrochloride ◽

Adrenergic Agonist ◽

Flow Probe ◽

Cyclic Monophosphate ◽

Synthase Inhibitor

Charan, Nirmal B., Shane R. Johnson, S. Lakshminarayan, William H. Thompson, and Paula Carvalho. Nitric oxide and β-adrenergic agonist-induced bronchial arterial vasodilation. J. Appl. Physiol. 82(2): 686–692, 1997.—In anesthetized sheep, we measured bronchial blood flow (Q˙br) by an ultrasonic flow probe to investigate the interaction between inhaled nitric oxide (NO; 100 parts/million) given for 5 min and 5 ml of aerosolized isoetharine (1.49 × 10−2 M concentration). NO and isoetharine increased Q˙br from 26.5 ± 6.5 to 39.1 (SE) ± 10.6 and 39.7 ± 10.7 ml/min, respectively ( n = 5). Administration of NO immediately after isoetharine further increasedQ˙br to 57.3 ± 15.1 ml/min. NO synthase inhibitor N ω-nitro-l-arginine methyl ester hydrochloride (l-NAME; 30 mg/kg, in 20 ml saline given iv) decreased Q˙br to 14.6 ± 2.6 ml/min. NO given three times alternately with isoetharine progressively increased Q˙br from 14.6 ± 2.6 to 74.3 ± 17.0 ml/min, suggesting that NO and isoetharine potentiate vasodilator effects of each other. In three other sheep, afterl-NAME, three sequential doses of isoetharine increased Q˙br from 10.2 ± 3.4 to 11.5 ± 5.7, 11.7 ± 4.7, and 13.3 ± 5.7 ml/min, respectively, indicating that effects of isoetharine are predominantly mediated through synthesis of NO. When this was followed by three sequential administrations of NO, Q˙br increased by 146, 172, and 185%, respectively. Thus in the bronchial circulation there seems to be a close interaction between adenosine 3′,5′-cyclic monophosphate- and guanosine 3′,5′-cyclic monophosphate-mediated vasodilatation.

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Effects of N ω- Nitro-L-arginine methyl ester hydrochloride on nitric oxide synthase expression in rabbit sublingual glands

Journal of Environmental Biology ◽

10.22438/jeb/40/5(si)/si-03 ◽

2019 ◽

Vol 40 (5(SI)) ◽

pp. 841-846

Author(s):

D.S. Kim ◽

◽

Y.H. Yu ◽

K.H. Lee ◽

J.H. Kang ◽

...

Keyword(s):

Nitric Oxide ◽

Methyl Ester ◽

Nitric Oxide Synthase ◽

Ester Hydrochloride ◽

Methyl Ester Hydrochloride ◽

Oxide Synthase

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A role for calcium-calmodulin in regulating nitric oxide production during skeletal muscle satellite cell activation

AJP Cell Physiology ◽

10.1152/ajpcell.00471.2008 ◽

2009 ◽

Vol 296 (4) ◽

pp. C922-C929 ◽

Cited By ~ 30

Author(s):

Ryuichi Tatsumi ◽

Adam L. Wuollet ◽

Kuniko Tabata ◽

Shotaro Nishimura ◽

Shoji Tabata ◽

...

Keyword(s):

Nitric Oxide ◽

Skeletal Muscle ◽

Methyl Ester ◽

Satellite Cell ◽

Satellite Cells ◽

Cell Activation ◽

Calcium Ionophore ◽

Ester Hydrochloride ◽

Methyl Ester Hydrochloride ◽

Satellite Cell Activation

When skeletal muscle is stretched or injured, myogenic satellite cells are activated to enter the cell cycle. This process depends on nitric oxide (NO) production by NO synthase (NOS), matrix metalloproteinase activation, release of hepatocyte growth factor (HGF) from the extracellular matrix, and presentation of HGF to the c-met receptor as demonstrated by a primary culture and in vivo assays. We now add evidence that calcium-calmodulin is involved in the satellite cell activation cascade in vitro. Conditioned medium from cultures that were treated with a calcium ionophore (A23187, ionomycin) for 2 h activated cultured satellite cells and contained active HGF, similar to the effect of mechanical stretch or NO donor treatments. The response was abolished by addition of calmodulin inhibitors (calmidazolium, W-13, W-12) or a NOS inhibitor NG-nitro-l-arginine methyl ester hydrochloride but not by its less inactive enantiomer NG-nitro-d-arginine methyl ester hydrochloride. Satellite cells were also shown to express functional calmodulin protein having a calcium-binding activity at 12 h postplating, which is the time at which the calcium ionophore was added in this study and the stretch treatment was applied in our previous experiments. Therefore, results from these experiments provide an additional insight that calcium-calmodulin mediates HGF release from the matrix and that this step in the activation pathway is upstream from NO synthesis.

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The Effects of the Heat Shock Protein 90 Inhibitor 17-Allylamino-17-Demethoxygeldanamycin, Cannabinoid Agonist WIN 55,212-2, and Nitric Oxide Synthase Inhibitor Nω-Nitro-L-Arginine Methyl Ester Hydrochloride on the Serotonin and Dry Skin-Induced Itch

International Archives of Allergy and Immunology ◽

10.1159/000520509 ◽

2021 ◽

pp. 1-10

Author(s):

Zeynep Gizem Todurga Seven ◽

Fatma Kubra Tombulturk ◽

Selim Gokdemir ◽

Sibel Ozyazgan

Keyword(s):

Nitric Oxide ◽

Heat Shock ◽

Methyl Ester ◽

Heat Shock Protein ◽

Heat Shock Protein 90 ◽

Ester Hydrochloride ◽

Methyl Ester Hydrochloride ◽

Synthase Inhibitor ◽

Cannabinoid Agonist ◽

Antipruritic Effect

Introduction: In many types of itch, the interaction between immune system cells, keratinocytes, and sensory nerves involved in the transmission of itch is quite complex. Especially for patients with chronic itching, current treatments are insufficient, and their quality of life deteriorates significantly. Objective: In this study, we aimed to investigate the role of the heat shock protein 90 (Hsp90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), cannabinoid agonist WIN 55,212-2, and nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) in pruritus. Methods: We created a serotonin (5-HT)-induced (50 μg/μL/mouse, i.d.) acute and acetone-ether-water (AEW)-induced chronic itching models. 17-AAG (1, 3, and 5 mg/kg, intraperitoneally [i.p.]), WIN 55,212-2 (1 mg/kg, i.p.), and L-NAME (1 mg/kg, i.p.) were applied to Balb/c mice. Results: We found that 17-AAG suppressed the scratches of mice, depending on the dose. The itch behavior was reduced by WIN 55,212-2, but L-NAME showed no antipruritic effect at the administered dose. The combined application of these agents in both pruritus models showed synergism in terms of the antipruritic effect. Our results showed that NO did not play a role in the antipruritic effect of WIN 55,212-2 and 17-AAG. Increased plasma IgE levels with AEW treatment decreased with the administration of 17-AAG (5 mg/kg, i.p.) and WIN 55,212-2. Conclusion: These results demonstrate that Hsp90 may play a role in the peripheral pathway of pruritus, and cannabinoid agonists and Hsp90 inhibitors can be used together in the treatment of pruritus.

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