Nitric Oxide is a Mediator of the Late-Phase Response in an Animal Model of Nasal Allergy

2000 ◽  
Vol 122 (5) ◽  
pp. 706-711 ◽  
Author(s):  
William F. Durland ◽  
Andrew P. Lane ◽  
Kimberly W. Durland ◽  
Timothy L. Smith ◽  
Kenneth L. Johnson ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Inflammatory Cell ◽  
Late Phase ◽  
Phase Response ◽  
Brown Norway ◽  
Nasal Allergy ◽  
Synthase Inhibitor ◽  
Histamine Challenge

The presence of nitric oxide (NO) in the nose is well documented; however, the role of this molecule in nasal physiology is still poorly understood. Our laboratory has previously demonstrated that NO is a mediator of the immediate secretory response to an intranasal histamine challenge in a rat model of nasal allergy. Histamine challenge, however, does not elicit a late-phase response (LPR). To study the role of NO in the LPR, we developed a model of nasal allergy in which brown Norway rats are actively sensitized to the allergen ovalbumin and later challenged intranasally with either phosphate-buffered saline solution (vehicle), ovalbumin in vehicle, or ovalbumin and the NO synthase inhibitor N-nitro-L-arginine methyl ester. In each experiment, nasal lavage samples were collected 30, 120, 240, and 360 minutes after challenge. Lavage samples were analyzed for albumin content by ELISA, inflammatory cell concentration with a hemocytometer, and evidence of inflammation by light microscopy. Blocking NO synthesis with N-nitro-L-arginine methyl ester significantly inhibited both albumin exudation and inflammatory cell influx into the nasal cavity during the LPR. These data suggest that NO plays a role in the LPR of nasal allergy.

Nitric oxide is a mediator of the late-phase response in an animal model of nasal allergy

2000 ◽  
Vol 122 (5) ◽  
pp. 706-711
Author(s):  
William F. Durland ◽  
Andrew P. Lane ◽  
Kimberly W. Durland ◽  
Timothy L. Smith ◽  
Kenneth L. Johnson ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Inflammatory Cell ◽  
Late Phase ◽  
Phase Response ◽  
Brown Norway ◽  
Nasal Allergy ◽  
Synthase Inhibitor ◽  
Histamine Challenge

The presence of nitric oxide (NO) in the nose is well documented; however, the role of this molecule in nasal physiology is still poorly understood. Our laboratory has previously demonstrated that NO is a mediator of the immediate secretory response to an intranasal histamine challenge in a rat model of nasal allergy. Histamine challenge, however, does not elicit a late-phase response (LPR). To study the role of NO in the LPR, we developed a model of nasal allergy in which brown Norway rats are actively sensitized to the allergen ovalbumin and later challenged intranasally with either phosphatebuffered saline solution (vehicle), ovalbumin in vehicle, or ovalbumin and the NO synthase inhibitor N-nitro-L-arginine methyl ester. In each experiment, nasal lavage samples were collected 30, 120, 240, and 360 minutes after challenge. Lavage samples were analyzed for albumin content by ELISA, inflammatory cell concentration with a hemocytometer, and evidence of inflammation by light microscopy. Blocking NO synthesis with N-nitro-L-arginine methyl ester significantly inhibited both albumin exudation and inflammatory cell influx into the nasal cavity during the LPR. These data suggest that NO plays a role in the LPR of nasal allergy.

scholarly journals Role of Nitric Oxide in Regulating Cerebrocortical Oxygen Consumption and Blood Flow during Hypercapnia

1994 ◽  
Vol 14 (3) ◽  
pp. 503-509 ◽  
Author(s):  
Ildiko Horvath ◽  
Norbert T. Sandor ◽  
Zoltan Ruttner ◽  
Alan C. McLaughlin
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Methyl Ester ◽  
Superior Sagittal Sinus ◽  
No Synthase ◽  
Sagittal Sinus ◽  
No Synthase Inhibitor ◽  
Synthase Inhibitor

The effect of the nitric oxide (NO) synthase inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) on the response of cerebrocortical oxygen consumption (CMRO2) and blood flow (CBF) to two levels of hypercapnia (Paco2 ∼ 60 mm Hg and Paco2 ∼ 90 mm Hg) was investigated in ketamine-anesthetized rats. CBF was calculated using the Kety–Schmidt approach and CMRO2 was calculated from the product of CBF and the arteriovenous (superior sagittal sinus) difference for oxygen. l-NAME treatment did not have a significant effect on either CMRO2 or CBE under normocapnic conditions but inhibited the hypercapnic increase of CMRO2 and the hypercapnic increase in CBF. These results suggest that NO plays a role in the response of CMRO2 and CBF during hypercapnia and are consistent with the suggestion that at least part of the increase in CBF observed during hypercapnia is coupled to an increase in CMRO2.

Disruption of renal peritubular blood flow in lipopolysaccharide-induced renal failure: role of nitric oxide and caspases

2005 ◽  
Vol 289 (6) ◽  
pp. F1324-F1332 ◽  
Author(s):  
Manish M. Tiwari ◽  
Robert W. Brock ◽  
Judit K. Megyesi ◽  
Gur P. Kaushal ◽  
Philip R. Mayeux
Keyword(s):  
Nitric Oxide ◽  
Renal Failure ◽  
Blood Flow ◽  
Saline Group ◽  
No Production ◽  
Capillary Perfusion ◽  
Peritubular Capillary ◽  
Synthase Inhibitor ◽  
Peritubular Capillary Perfusion

Acute renal failure (ARF) is a frequent and serious complication of endotoxemia caused by lipopolysaccharide (LPS) and contributes significantly to mortality. The present studies were undertaken to examine the roles of nitric oxide (NO) and caspase activation on renal peritubular blood flow and apoptosis in a murine model of LPS-induced ARF. Male C57BL/6 mice treated with LPS ( Escherichia coli) at a dose of 10 mg/kg developed ARF at 18 h. Renal failure was associated with a significant decrease in peritubular capillary perfusion. Vessels with no flow increased from 7 ± 3% in the saline group to 30 ± 4% in the LPS group ( P < 0.01). Both the inducible NO synthase inhibitor l- N6-1-iminoethyl-lysine (l-NIL) and the nonselective caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (Z-VAD) prevented renal failure and reversed perfusion deficits. Renal failure was also associated with an increase in renal caspase-3 activity and an increase in renal apoptosis. Both l-NIL and Z-VAD prevented these changes. LPS caused an increase in NO production that was blocked by l-NIL but not by Z-VAD. Taken together, these data suggest NO-mediated activation of renal caspases and the resulting disruption in peritubular blood flow are an important mechanism of LPS-induced ARF.

Nitric oxide and cerebral blood flow responses to hyperbaric oxygen

2000 ◽  
Vol 88 (4) ◽  
pp. 1381-1389 ◽  
Author(s):  
Ivan T. Demchenko ◽  
Albert E. Boso ◽  
Thomas J. O'Neill ◽  
Peter B. Bennett ◽  
Claude A. Piantadosi
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Methyl Ester ◽  
No Production ◽  
No Donors ◽  
Mk 801 ◽  
Neuronal Excitation ◽  
Synthase Inhibitor ◽  
Electroencephalogram Eeg

We have tested the hypothesis that cerebral nitric oxide (NO) production is involved in hyperbaric O2 (HBO2) neurotoxicity. Regional cerebral blood flow (rCBF) and electroencephalogram (EEG) were measured in anesthetized rats during O2 exposure to 1, 3, 4, and 5 ATA with or without administration of the NO synthase inhibitor ( N ω-nitro-l-arginine methyl ester), l-arginine, NO donors, or the N-methyl-d-aspartate receptor inhibitor MK-801. After 30 min of O2 exposure at 3 and 4 ATA, rCBF decreased by 26–39% and by 37–43%, respectively, and was sustained for 75 min. At 5 ATA, rCBF decreased over 30 min in the substantia nigra by one-third but, thereafter, gradually returned to preexposure levels, preceding the onset of EEG spiking activity. Rats pretreated with N ω-nitro-l-arginine methyl ester and exposed to HBO2 at 5 ATA maintained a low rCBF. MK-801 did not alter the cerebrovascular responses to HBO2at 5 ATA but prevented the EEG spikes. NO donors increased rCBF in control rats but were ineffective during HBO2 exposures. The data provide evidence that relative lack of NO activity contributes to decreased rCBF under HBO2, but, as exposure time is prolonged, NO production increases and augments rCBF in anticipation of neuronal excitation.

Role of NO in goat basal cerebral circulation and after vasodilatation to hypercapnia or brief ischemias

1993 ◽  
Vol 265 (6) ◽  
pp. R1410-R1415 ◽  
Author(s):  
G. Dieguez ◽  
J. L. Garcia ◽  
N. Fernandez ◽  
A. L. Garcia-Villalon ◽  
L. Monge ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
Methyl Ester ◽  
Cerebral Circulation ◽  
Systemic Arterial Pressure ◽  
Nitric Oxide Production ◽  
Hemodynamic Effects ◽  
Arterial Pco2 ◽  
Different Levels

The role of nitric oxide (NO) in the cerebral circulation under basal conditions and after vasodilatation to hypercapnia or reactive hyperemias was studied in 17 anesthetized goats. The intravenous administration of NG-nitro-L-arginine methyl ester (L-NAME, 3-4 or 8-10 mg/kg), an inhibitor of nitric oxide production, reduced middle cerebral artery (MCA) flow (electromagnetically measured) by 19 and 30% and increased systemic arterial pressure by 21 and 26%, respectively, whereas heart rate did not significantly change; MCA resistance increased by 48 and 86%, respectively. These hemodynamic effects were reversed by L-arginine (200-300 mg/kg iv; 5 goats). Different levels of hypercapnia (PCO2 of 30-35, 40-45, and 55-65 mmHg) (12 goats) produced arterial PCO2-dependent increases in MCA flow that were similar under control and L-NAME treatment. Graded cerebral hyperemia occurred after 5, 10, and 20 s of MCA occlusion in 5 goats, but its magnitude was decreased during L-NAME treatment. It suggests that, in the cerebral circulation, nitric oxide 1) produces a basal vasodilator tone and 2) is probably not involved in the vasodilatation to hypercapnia but may mediate hyperemic responses after short brain ischemias.

scholarly journals Vasoactivity of adenosine in the trout (Oncorhynchus mykiss) coronary system: involvement of nitric oxide and interaction with noradrenaline

1998 ◽  
Vol 201 (22) ◽  
pp. 3075-3083 ◽  
Author(s):  
T Mustafa ◽  
C Agnisola
Keyword(s):  
Nitric Oxide ◽  
Constant Pressure ◽  
Constant Flow ◽  
Nitric Oxide Synthase Inhibitor ◽  
Heart Preparation ◽  
Synthase Inhibitor ◽  
Coronary Endothelium ◽  
Oxide Synthase ◽  
Working Heart

A vasoconstrictory response to adenosine has been reported in coronary rings from fish. Since the reactivity of the large coronary arteries and the microcirculation may differ, the present study was undertaken to determine the role of adenosine in the intact coronary system of trout under constant pressure or flow using an isolated and non-working heart preparation. The involvement of nitric oxide (NO) and the interaction with noradrenaline were also studied. At 10(-9) to 10(-8 )mol l-1, adenosine caused a vasoconstrictory response, whereas between 10(-7) and 10(-5 )mol l-1 the response was predominantly vasodilative. Theophylline abolished both these responses to adenosine. The vasodilation induced by adenosine (at 10(-5 )mol l-1) was significantly reduced when the preparation was perfused under constant-flow than rather under constant-pressure conditions. The nitric oxide synthase inhibitor N-nitro-l-arginine (l-NA, 10(-4 )mol l-1) partially reduced the vasodilation induced by adenosine (at 10(-5 )mol l-1) under constant-pressure but not under constant-flow conditions. Perfusion of the intact coronary system with l-arginine or with adenosine significantly increased the rate of nitrite (NO2-) release, while perfusion with l-NA or theophylline reduced NO2- release. Chemical denudation of the coronary endothelium by CHAPS resulted in the loss of both the l-arginine- and adenosine-mediated vasodilation and the l-arginine-induced increase in the rate of NO2- release. Adenosine (10(-5 )mol l-1) offset and overrode the vasoconstriction induced by 10(-7 )mol l-1 noradrenaline. l-NA inhibited only the adenosine-induced vasodilation but not the ability to offset noradrenaline vasoconstriction, excluding the involvement of NO in the interaction between adenosine and noradrenaline.

Abstract 16720: Cytoglobin Regulates Cardiovascular Function and Vessel Tone by Controlling the Rate of Vascular Nitric Oxide Metabolism

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Xiaoping Liu ◽  
Mohamed A El-Mahdy ◽  
Raed S Ismail ◽  
Sean Little ◽  
Le T Thuy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Wall ◽  
No Donor ◽  
Nitric Oxide Metabolism ◽  
No Consumption ◽  
Potent Vasodilator ◽  
Inner Diameter ◽  
The Difference ◽  
Synthase Inhibitor

Cytoglobin (Cygb) can effectively metabolize nitric oxide (NO), a potent vasodilator, in the presence of oxygen and reductants. Cygb in the vascular wall may affect cardiovascular functions by changing the rate of NO metabolism. In this study, we directly tested the vascular role of Cygb using Cygb knockout (Cygb-/-) mice. The mean blood pressure of Cygb-/- and C57BL/6 wild type (WT) mice was 65.3 ± 1.9 mmHg and 93.7 ± 1.5 mmHg, respectively (n=10). Using echocardiography, we observed that cardiac output (CO) was increased in Cygb-/- mice compared to WT with values of 29.8 ± 3.9 vs 17.7 ± 0.9 ml/min. The systemic vascular resistance (SVR) of Cygb-/- mice was decreased by ~60% vs that of WT mice (Fig. 1). Further, the inner diameter (id) of aorta of Cygb-/- mice was dilated compared to WT with values of 2.2 ± 0.1 mm vs 1.5 ± 0.05 mm (n=5), respectively. After treatment with the NO synthase inhibitor L-NAME, no difference in the aortic id remained between Cygb-/- (1.55 ± 0.03 mm) and WT (1.49 ± 0.02 mm) mice, indicating that the NO pathway is responsible for the difference in vascular inner diameters and tone. Myograph experiments show that the aortic vasodilation response of Cygb-/- mice is much more sensitive to acetylcholine (Ach) or the NO donor nitroprusside (SNP) (EC50 shifts from 13 nM and 2.9 nM (WT mice) to 0.33 nM and 0.16 nM (Cygb-/-) for Ach and SNP, respectively). Using NO electrodes to measure the rate of NO consumption by SMCs and quantitative imunoblotting to estimate Cygb content in RSMCs-AR and Cygb knockdown RSMCs, we observed that 90% of NO consumption by RSMCs-AR is caused by the intracellular Cygb. Our results indicate that Cygb deficiency in the vascular wall of Cygb-/- mice greatly reduces the rate of NO metabolism and increases vascular NO concentration, resulting in vasodilation, increase in vessel lumen diameter, and decrease in SVR. These results demonstrate that Cygb regulates cardiac function and vessel tone by controlling the rate of vascular NO metabolism.

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