ArticleNeonatology2012
Role of arginase in impairing relaxation of lung parenchyma of hyperoxia-exposed neonatal rats.
Article in Neonatology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- The role of prophylactic arginine supplementation for prevention of bronchopulmonary dysplasia in extremely preterm infants.Journal of perinatology : official journal of the California Perinatal Association · 2026Article
- Polymeric nanoparticle-mediated siRNA delivery into primary human bronchial airway cells.American journal of physiology. Cell physiology · 2026Article
- Inhibition of Rho-kinase restores impaired relaxation of airway smooth muscle in rat pups exposed to neonatal hyperoxia.Physiological reports · 2026Article
- Protective Effects of Resveratrol Against Airway Hyperreactivity, Oxidative Stress, and Lung Inflammation in a Rat Pup Model of Bronchopulmonary Dysplasia.Physiological research · 2024Article
- Quercetin supplementation attenuates airway hyperreactivity and restores airway relaxation in rat pups exposed to hyperoxia.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Metabolic dysregulation in bronchopulmonary dysplasia: Implications for identification of biomarkers and therapeutic approaches.Redox biology · 2021Article
- Arginine Therapy for Lung Diseases.Frontiers in pharmacology · 2021Review
- Calcium-Sensing Receptor Contributes to Hyperoxia Effects on Human Fetal Airway Smooth Muscle.Frontiers in physiology · 2021Article
- Hydrogen sulfide, oxygen, and calcium regulation in developing human airway smooth muscle.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Curcumin analogs (B2BrBC and C66) supplementation attenuates airway hyperreactivity and promote airway relaxation in neonatal rats exposed to hyperoxia.Physiological reports · 2020Article
- Class C GPCRs in the airway.Current opinion in pharmacology · 2020Review
- S-Nitrosoglutathione Attenuates Airway Hyperresponsiveness in Murine Bronchopulmonary Dysplasia.Molecular pharmacology · 2016Article
- Soluble guanylate cyclase modulators blunt hyperoxia effects on calcium responses of developing human airway smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Perinatal oxygen in the developing lung.Canadian journal of physiology and pharmacology · 2015Review
- Severity of neonatal hyperoxia determines structural and functional changes in developing mouse airway.American journal of physiology. Lung cellular and molecular physiology · 2014Article
- Arginase 2 deficiency prevents oxidative stress and limits hyperoxia-induced retinal vascular degeneration.PloS one · 2014Article
- Immunohistochemical detection of arginase-I expression in formalin-fixed lung and other tissues.Journal of histotechnology · 2013Article
- Intra-amniotic LPS amplifies hyperoxia-induced airway hyperreactivity in neonatal rats.Pediatric research · 2013Article
- Moderate tidal volumes and oxygen exposure during initiation of ventilation in preterm fetal sheep.Pediatric research · 2012Article
- Can nitric oxide-based therapy prevent bronchopulmonary dysplasia?Clinics in perinatology · 2012Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundProlonged exposure of immature lungs to hyperoxia contributes to neonatal lung injury and airway hyperreactivity. We have previously demonstrated that neonatal exposure of rat pups to ≥95% O2 impairs airway relaxation due to disruption of nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling.
objectiveWe now hypothesize that these impaired relaxation responses are secondary to hyperoxia-induced upregulation of arginase, which competes with NO synthase for L-arginine.
methodsRat pups were exposed to moderate neonatal hyperoxia (50% O2) or room air for 7 days from birth. In additional hyperoxic and room air groups, exogenous L-arginine (300 mg/kg/day i.p.) or arginase inhibitor (Nω-hydroxy-nor-arginine, 30 mg/kg/day i.p.) were administered daily. After 7 days, animals were anesthetized and sacrificed either for preparation of lung parenchymal strips or lung perfusion.
resultsIn response to electrical field stimulation (EFS), bethanechol-preconstricted lung parenchymal strips from hyperoxic pups exhibited significantly reduced relaxation compared to room air controls. Supplementation of L-arginine or arginase blockade restored hyperoxia-induced impairment of relaxation. Expression of arginase I in airway epithelium was increased in response to hyperoxia but reduced by arginase blockade. Arginase activity was also significantly increased in hyperoxic lungs as compared to room air controls and reduced following arginase blockade. EFS-induced production of NO was decreased in hyperoxia-exposed airway smooth muscle and restored by arginase blockade.
conclusionThese data suggest that NO-cGMP signaling is disrupted in neonatal rat pups exposed to even moderate hyperoxia due to increased arginase activity and consequent decreased bioavailability of the substrate L-arginine. We speculate that supplementation of arginine and/or inhibition of arginase may be a useful therapeutic tool to prevent or treat neonatal lung injury.
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