Inhaled nitric oxide attenuates hyperoxic and inflammatory injury without alteration of phosphatidylcholine synthesis in rat lungs

Inhaled nitric oxide (iNO) is commonly used in the treatment of very ill pre-term newborns. Previous studies showed that exogenous NO could affect endothelial NO synthase (eNOS) activity and expression in vascular endothelial cell cultures or adult rat models, but this has never been fully described in newborn rat lungs. We therefore aimed to assess the effects of iNO on eNOS expression and activity in newborn rats.Rat pups, post-natal day (P) 0 to P7, and their dams were placed in a chamber containing NO at 5 ppm (iNO-5 ppm group) or 20 ppm (iNO-20 ppm group), or in room air (control group). Rat pups were sacrificed at P7 and P14 for evaluation of lung eNOS expression and activity.At P7, eNOS protein expression in total lung lysates, in bronchial and arterial sections, was significantly decreased in the iNO-20 ppm versus control group. At P14, eNOS expression was comparable among all three groups. The amounts of eNOS mRNA significantly differed at P7 between the iNO-20 ppm and control groups. NOS activity decreased in the iNO-20 ppm group at P7 and returned to normal levels at P14. There was an imbalance between superoxide dismutase and NOS activities in the iNO-20 ppm group at P7.Inhalation of NO at 20 ppm early after birth decreases eNOS gene transcription, protein expression and enzyme activity. This decrease might account for the rebound phenomenon observed in patients treated with iNO.

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Inhaled Nitric Oxide Increases Hydroxyl Radical Production in Rat Lungs.† 1554

Pediatric Research ◽

10.1203/00006450-199704001-01573 ◽

1997 ◽

Vol 41 ◽

pp. 261-261

Author(s):

Leif D Nelin ◽

James F Morrisey ◽

Richard M Effros ◽

Ralph M Schapira

Keyword(s):

Nitric Oxide ◽

Hydroxyl Radical ◽

Inhaled Nitric Oxide ◽

Radical Production ◽

Rat Lungs

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E4021, a Selective Phosphodiesterase 5 Inhibitor, Potentiates the Vasodilator Effect of Inhaled Nitric Oxide in Isolated Perfused Rat Lungs

Journal of Cardiovascular Pharmacology ◽

10.1097/00005344-199904000-00015 ◽

1999 ◽

Vol 33 (4) ◽

pp. 619-624 ◽

Cited By ~ 7

Author(s):

Masahiro Ohnishi ◽

Masahiko Oka ◽

Masashi Muramatsu ◽

Koichi Sato ◽

Shiro Kira ◽

...

Keyword(s):

Nitric Oxide ◽

Inhaled Nitric Oxide ◽

Vasodilator Effect ◽

Phosphodiesterase 5 Inhibitor ◽

Rat Lungs ◽

Phosphodiesterase 5

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Inhaled Nitric Oxide Ameliorates Ischemia-reperfusion Lung Injury in Rat Lungs From Non-heart-beating Donor

CHEST Journal ◽

10.1378/chest.124.4_meetingabstracts.201s-c ◽

2003 ◽

Vol 124 (4) ◽

pp. 201S

Author(s):

Seiki Takashima ◽

Giovanna Koukoulis ◽

Thomas M. Egan

Keyword(s):

Nitric Oxide ◽

Lung Injury ◽

Ischemia Reperfusion ◽

Inhaled Nitric Oxide ◽

Rat Lungs ◽

Heart Beating

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Preconditioning by inhaled nitric oxide prevents hyperoxic and ischemia/reperfusion injury in rat lungs

Pulmonary Pharmacology & Therapeutics ◽

10.1016/j.pupt.2007.10.005 ◽

2008 ◽

Vol 21 (2) ◽

pp. 418-429 ◽

Cited By ~ 10

Author(s):

Thomas Waldow ◽

Wolfgang Witt ◽

André Ulmer ◽

Andreas Janke ◽

Konstantin Alexiou ◽

...

Keyword(s):

Nitric Oxide ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Inhaled Nitric Oxide ◽

Rat Lungs

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Sites of vasodilation by inhaled nitric oxide vs. sodium nitroprusside in endothelin-constricted isolated rat lungs

Journal of Applied Physiology ◽

10.1152/jappl.1994.77.1.51 ◽

1994 ◽

Vol 77 (1) ◽

pp. 51-57 ◽

Cited By ~ 37

Author(s):

C. M. Roos ◽

G. F. Rich ◽

D. R. Uncles ◽

M. O. Daugherty ◽

D. U. Frank

Keyword(s):

Nitric Oxide ◽

Sodium Nitroprusside ◽

Pulmonary Veins ◽

Inhaled Nitric Oxide ◽

Large Artery ◽

Rat Lungs ◽

Large Vein ◽

Arteries And Veins ◽

Inhaled No ◽

Isolated Rat

We localized the sites of vasodilation of inhaled nitric oxide (NO), a selective pulmonary vasodilator, and sodium nitroprusside (SNP) in isolated rat lungs. The sites were determined by analyzing the arterial, venous, and double-occlusion data with a two-resistor (small arteries and veins) three-capacitor (large arteries, large veins, and capillaries) model of the pulmonary vascular bed. Inhaled NO (170 and 670 ppm) and SNP (22.5 and 45.0 micrograms) decreased the small-artery resistance by 7.4 +/- 1.6, 17.2 +/- 2.2, 14.2 +/- 2.8, and 21.4 +/- 3.4% and the small-vein resistance by 13.5 +/- 3.2, 20.3 +/- 3.4 (SNP of 22.5 micrograms not significant), and 9.3 +/- 3.3%, respectively, in blood-perfused lungs (n = 12). Similar results were observed in Krebs-perfused lungs (n = 12). Capillary compliance was unaffected by inhaled NO and SNP. SNP increased the large-artery capacitance by 40.0 +/- 8.6 and 69.3 +/- 9.7%, whereas inhaled NO had no effect. SNP increased the large-vein capacitance by 31.0 +/- 8.7 and 48.0 +/- 10.7%, whereas inhaled NO had no effect in blood-perfused lungs. However, in Krebs-perfused lungs inhaled NO and SNP (45.0 micrograms only) increased the large-vein capacitance by 43.3 +/- 11.9, 41.4 +/- 14.2, and 44.2 +/- 11.0%. In conclusion, in blood-perfused isolated rat lungs inhaled NO and SNP dilate small-resistance arteries and veins, whereas SNP but not inhaled NO dilates larger capacitance arteries and veins. Furthermore, blood appears to prevent the downstream vasodilation by inhaled NO on larger capacitance pulmonary veins.

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