Inhaled nitric oxide increases surfactant protein gene expression in the  intact lamb

Inhaled nitric oxide (iNO) is used to treat a number of disease processes. Although in vitro data suggest that nitric oxide (NO) alters surfactant protein gene expression, the effects in vivo have not been studied. The objective of this study was to evaluate the effects of iNO on surfactant protein (SP)-A, -B, and -C gene expression in the intact lamb. Thirteen 4-wk-old lambs were mechanically ventilated with 21% oxygen and received iNO at 40 ppm ( n = 7) or vehicle gas ( n = 6) for 24 h. Peripheral lung biopsies were obtained at 0, 12, and 24 h and analyzed for surfactant mRNA, protein, and total DNA content. Inhaled NO increased SP-A and SP-B mRNA content by 80% from 0 to 12 h and by 78 and 71%, respectively, from 0 to 24 h. There was an increase in SP-A and SP-B protein content by 45% from 0 to 12 h, and a decrease by 70 and 65%, respectively, from 0 to 24 h. DNA content was unchanged. The mechanisms and physiological effects of these findings warrant further investigation.

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Nitric oxide decreases surfactant protein gene expression in primary cultures of type II pneumocytes

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00210.2004 ◽

2005 ◽

Vol 288 (5) ◽

pp. L950-L957 ◽

Cited By ~ 11

Author(s):

Jae W. Lee ◽

Robert F. Gonzalez ◽

Cheryl J. Chapin ◽

Justin Busch ◽

Jeffrey R. Fineman ◽

...

Keyword(s):

Gene Expression ◽

Nitric Oxide ◽

Protein Gene ◽

Surfactant Protein ◽

Model Systems ◽

Cell Phenotype ◽

Mrna Levels ◽

Type Ii ◽

Endothelin 1 ◽

Type Ii Pneumocytes

Inhaled nitric oxide (NO) is a selective pulmonary vasodilator effective in treating persistent pulmonary hypertension in newborns and in infants following congenital heart disease surgery. Recently, multiple in vivo and in vitro studies have shown a negative effect of NO on surfactant activity as well as surfactant protein gene expression. Although the relationship between NO and surfactant has been studied previously, the data has been hard to interpret due to the model systems used. The objective of the current study was to characterize the effect of NO on surfactant protein gene expression in primary rat type II pneumocytes cultured on a substratum that promoted the maintenance of type II cell phenotype. Exposure to a NO donor, S-nitroso-N-acetylpenicillamine (SNAP), decreased surfactant protein (SP)-A, (SP)-B, and (SP)-C mRNA levels in type II pneumocytes in a time- and dose-dependent manner. The effect was mediated in part by an increase in endothelin-1 secretion and a decrease in the intracellular messenger, phosphorylated ERK1/2 mitogen-activated protein kinases (MAPK). Exposing type II pneumocytes to endothelin-1 receptor antagonists PD-156707 or bosentan before exposure to SNAP partially prevented the decrease in surfactant protein gene expression. The results showed that NO mediated the decrease in surfactant protein gene expression at least in part through an increase in endothelin-1 secretion and a decrease in phosphorylated ERK1/2 MAPKs.

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Inhaled nitric oxide inhibits NOS activity in lambs: potential mechanism for rebound pulmonary hypertension

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1999.277.5.h1849 ◽

1999 ◽

Vol 277 (5) ◽

pp. H1849-H1856 ◽

Cited By ~ 23

Author(s):

Stephen M. Black ◽

R. Scott Heidersbach ◽

D. Michael McMullan ◽

Janine M. Bekker ◽

Michael J. Johengen ◽

...

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Pulmonary Vascular Resistance ◽

Vascular Resistance ◽

Inhaled Nitric Oxide ◽

Protein Levels ◽

Acute Withdrawal ◽

Inhaled No

Life-threatening increases in pulmonary vascular resistance have been noted on acute withdrawal of inhaled nitric oxide (NO), although the mechanisms remain unknown. In vitro data suggest that exogenous NO exposure inhibits endothelial NO synthase (NOS) activity. Thus the objectives of this study were to determine the effects of inhaled NO therapy and its acute withdrawal on endogenous NOS activity and gene expression in vivo in the intact lamb. Six 1-mo-old lambs were mechanically ventilated and instrumented to measure vascular pressures and left pulmonary blood flow. Inhaled NO (40 ppm) acutely decreased left pulmonary vascular resistance by 27.5 ± 4.7% ( P < 0.05). This was associated with a 207% increase in plasma cGMP concentrations ( P < 0.05). After 6 h of inhaled NO, NOS activity was reduced to 44.3 ± 5.9% of pre-NO values ( P < 0.05). After acute withdrawal of NO, pulmonary vascular resistance increased by 52.1 ± 11.6% ( P < 0.05) and cGMP concentrations decreased. Both returned to pre-NO values within 60 min. One hour after NO withdrawal, NOS activity increased by 48.4 ± 19.1% to 70% of pre-NO values ( P < 0.05). Western blot analysis revealed that endothelial NOS protein levels remained unchanged throughout the study period. These data suggest a role for decreased endogenous NOS activity in the rebound pulmonary hypertension noted after acute withdrawal of inhaled NO.

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Inhaled Nitric Oxide Inhibits Human Platelet Aggregation, P-Selectin Expression, and Fibrinogen Binding In Vitro and In Vivo

Circulation ◽

10.1161/01.cir.97.15.1481 ◽

1998 ◽

Vol 97 (15) ◽

pp. 1481-1487 ◽

Cited By ~ 94

Author(s):

André Gries ◽

Christoph Bode ◽

Karlheinz Peter ◽

Axel Herr ◽

Hubert Böhrer ◽

...

Keyword(s):

Nitric Oxide ◽

Platelet Aggregation ◽

Human Platelet ◽

Inhaled Nitric Oxide ◽

Human Platelet Aggregation ◽

Fibrinogen Binding

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Mechanical stimuli induce vascular parathyroid hormone-related protein gene expression in vivo and in vitro.

Endocrinology ◽

10.1210/endo.134.5.8156926 ◽

1994 ◽

Vol 134 (5) ◽

pp. 2230-2236 ◽

Cited By ~ 37

Author(s):

C J Pirola ◽

H M Wang ◽

M I Strgacich ◽

A Kamyar ◽

B Cercek ◽

...

Keyword(s):

Gene Expression ◽

Parathyroid Hormone ◽

Protein Gene ◽

Mechanical Stimuli ◽

Related Protein ◽

Parathyroid Hormone Related Protein

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Rabbit surfactant protein C: cDNA cloning and regulation of alternatively spliced surfactant protein C mRNAs

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1992.263.6.l634 ◽

1992 ◽

Vol 263 (6) ◽

pp. L634-L644 ◽

Cited By ~ 6

Author(s):

V. Boggaram ◽

R. K. Margana

Keyword(s):

Gene Expression ◽

Lung Development ◽

Genomic Dna ◽

Protein C ◽

Fetal Lung ◽

Surfactant Protein ◽

Surfactant Protein C ◽

Fetal Lung Development ◽

Mrna Content

Surfactant protein C (SP-C), a hydrophobic protein of pulmonary surfactant is essential for surfactant function. Toward elucidating molecular mechanisms that mediate regulation of SP-C gene expression in rabbit lung, we isolated and characterized cDNAs encoding rabbit SP-C and studied the regulation of SP-C gene expression during fetal lung development and by adenosine 3',5'-cyclic monophosphate (cAMP) and dexamethasone in fetal lung tissues in vitro. We found that rabbit SP-C is highly homologous to SP-C of other species and is encoded by two mRNAs that differ by an insertion of 31 nucleotides in the 3' untranslated regions. SP-C mRNAs were classified into two types based on the nucleotide sequence; type I represents RNA without the 31 nucleotide insert and comprises approximately 80–90% of total SP-C mRNA content, whereas type II represents RNA containing the insert and comprises approximately 10–20% of total SP-C mRNA content. SP-C mRNAs were induced in a coordinate manner during fetal lung development and by cAMP and dexamethasone in fetal lung tissues in vitro. Southern hybridization analysis of genomic DNA suggested that SP-C mRNAs are encoded by a single gene. Polymerase [corrected] chain reaction-amplification of genomic DNA with oligonucleotide primers flanking the insertional sequence and sequence analysis of amplified DNA showed that SP-C mRNAs are produced by alternative use of 3' splice sites of intron 5 of SP-C gene.

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Thyroid Hormone Regulates Endogenous Amyloid-β Precursor Protein Gene Expression and Processing in Both In Vitro and In Vivo Models

Thyroid ◽

10.1089/thy.2006.16.1207 ◽

2006 ◽

Vol 16 (12) ◽

pp. 1207-1213 ◽

Cited By ~ 22

Author(s):

Stephen A. O'Barr ◽

Jin S. Oh ◽

Chan Ma ◽

Gregory A. Brent ◽

James J. Schultz

Keyword(s):

Gene Expression ◽

Thyroid Hormone ◽

Protein Gene ◽

Amyloid Β ◽

Precursor Protein ◽

In Vivo Models

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Inhaled Nitric Oxide for postexposure chemoprophylaxis of COVID-19

10.21203/rs.3.rs-612293/v1 ◽

2021 ◽

Author(s):

Antoine AbdelMassih ◽

Rafeef Hozaien ◽

Meryam El Shershaby ◽

Aya Kamel ◽

Habiba-Allah Ismail ◽

...

Keyword(s):

Nitric Oxide ◽

Systematic Review ◽

Viral Replication ◽

Medical Personnel ◽

Inhaled Nitric Oxide ◽

Cochrane Central Register ◽

Central Register ◽

Antiviral Role

Abstract Background: Postexposure prophylaxis has been an overlooked strategy in the context of COVID-19. Inhaled Nitric Oxide offers itself as a potential tool in this context. The aim of this systematic review was to depict previous in vivo and in vitro studies demonstrating an antiviral role for NO Methodology:Embase, Medline and the Cochrane Central Register were used to search for specific keywords such as “Nitric oxide” AND “Antiviral activity” for relevant publications up to 1st of June 2021. The systematic review was performed using PRISMA protocolResults:Twenty-one studies were identified depicting an antiviral role for Nitric Oxide. Those studies involved sixteen viruses. Only four of the depicted studies were clinical trials, while three were performed on a murine model. The remainder of the studies involved in vitro experimentation of the role of NO in halting viral replication of several viruses including SARS-CoV-2Conclusion: While early reports of NO role in the treatment of COVID-19 suggested its use for the treatment of established ARDS, NO seems to have a much earlier and more efficient prophylactic role. It inhibits a protease needed for canonical viral replication of SARS-CoV-2, namely Furin, by decreasing calcium's cytosolic levels. This might add a significant tool for postexposure chemoprophylaxis in the at-risk group, especially medical personnel.

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Inhaled nitric oxide induced NOS inhibition and rebound pulmonary hypertension: a role for superoxide and peroxynitrite in the intact lamb

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00019.2005 ◽

2006 ◽

Vol 290 (2) ◽

pp. L359-L366 ◽

Cited By ~ 37

Author(s):

Peter Oishi ◽

Albert Grobe ◽

Eileen Benavidez ◽

Boaz Ovadia ◽

Cynthia Harmon ◽

...

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Inhaled Nitric Oxide ◽

In Vivo Studies ◽

Acute Increase ◽

No Signaling ◽

Oxide Synthase ◽

Inhaled No

Previous in vivo studies indicate that inhaled nitric oxide (NO) decreases nitric oxide synthase (NOS) activity and that this decrease is associated with significant increases in pulmonary vascular resistance (PVR) upon the acute withdrawal of inhaled NO (rebound pulmonary hypertension). In vitro studies suggest that superoxide and peroxynitrite production during inhaled NO therapy may mediate these effects, but in vivo data are lacking. The objective of this study was to determine the role of superoxide in the decrease in NOS activity and rebound pulmonary hypertension associated with inhaled NO therapy in vivo. In control lambs, 24 h of inhaled NO (40 ppm) decreased NOS activity by 40% ( P < 0.05) and increased endothelin-1 levels by 64% ( P < 0.05). Withdrawal of NO resulted in an acute increase in PVR (60.7%, P < 0.05). Associated with these changes, superoxide and peroxynitrite levels increased more than twofold ( P < 0.05) following 24 h of inhaled NO therapy. However, in lambs treated with polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) during inhaled NO therapy, there was no change in NOS activity, no increase in superoxide or peroxynitrite levels, and no increase in PVR upon the withdrawal of inhaled NO. In addition, endothelial NOS nitration was 18-fold higher ( P < 0.05) in control lambs than in PEG-SOD-treated lambs following 24 h of inhaled NO. These data suggest that superoxide and peroxynitrite participate in the decrease in NOS activity and rebound pulmonary hypertension associated with inhaled NO therapy. Reactive oxygen species scavenging may be a useful therapeutic strategy to ameliorate alterations in endogenous NO signaling during inhaled NO therapy.

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