ArticlePulmonary medicine2016
Long-Term Chronic Intermittent Hypobaric Hypoxia in Rats Causes an Imbalance in the Asymmetric Dimethylarginine/Nitric Oxide Pathway and ROS Activity: A Possible Synergistic Mechanism for Altitude Pulmonary Hypertension?
Article in Pulmonary medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 56 citations in OpenAlex.
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- Altitude hypoxia and hypoxemia: pathogenesis and management.Signal transduction and targeted therapy · 2026Review
- Xinnaoxin tablets ameliorate high-altitude polycythemia-associated cardiac injury by regulating the NF-κB, MAPK, and PI3K/AKT signaling pathways.Frontiers in pharmacology · 2026Article
- Understanding the mechanistic and therapeutic perspectives on cytokines and chemokines in acute high-altitude illness syndromes.Journal of pharmaceutical analysis · 2025Review
- High-altitude pulmonary hypertension: a comprehensive review of mechanisms and management.Clinical and experimental medicine · 2025Review
- Dental pulp stem cells promote genioglossus repair and systemic amelioration in chronic intermittent hypoxia.iScience · 2024Article
- Facilitating Nitrite-Derived S-Nitrosothiol Formation in the Upper Gastrointestinal Tract in the Therapy of Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Rapid altitude displacement induce zebrafish appearing acute high altitude illness symptoms.Heliyon · 2024Article
- The effect of chronic intermittent hypobaric hypoxia improving liver damage in metabolic syndrome rats through ferritinophagy.Pflugers Archiv : European journal of physiology · 2023Article
- Common mechanisms underlying diabetic vascular complications: focus on the interaction of metabolic disorders, immuno-inflammation, and endothelial dysfunction.Cell communication and signaling : CCS · 2023Review
- The Effectiveness of L-arginine in Clinical Conditions Associated with Hypoxia.International journal of molecular sciences · 2023Review
- Molecular Mechanisms of High-Altitude Acclimatization.International journal of molecular sciences · 2023Review
- Asymmetric and symmetric dimethylarginine in high altitude pulmonary hypertension (HAPH) and high altitude pulmonary edema (HAPE).Frontiers in physiology · 2023Article
- Impact of Zinc on Oxidative Signaling Pathways in the Development of Pulmonary Vasoconstriction Induced by Hypobaric Hypoxia.International journal of molecular sciences · 2022Review
- Oxidative Stress and Diseases Associated with High-Altitude Exposure.Antioxidants (Basel, Switzerland) · 2022Review
- Dysregulation of the Nitric Oxide/Dimethylarginine Pathway in Hypoxic Pulmonary Vasoconstriction-Molecular Mechanisms and Clinical Significance.Frontiers in medicine · 2022Review
- Maladaptive Pulmonary Vascular Responses to Chronic Sustained and Chronic Intermittent Hypoxia in Rat.Antioxidants (Basel, Switzerland) · 2021Article
- Association of Genes of the NO Pathway with Altitude Disease and Hypoxic Pulmonary Hypertension.Journal of clinical medicine · 2021Article
- Exercise intervention under hypoxic condition as a new therapeutic paradigm for type 2 diabetes mellitus: A narrative review.World journal of diabetes · 2021Review
- Oxidative Stress, Kinase Activation, and Inflammatory Pathways Involved in Effects on Smooth Muscle Cells During Pulmonary Artery Hypertension Under Hypobaric Hypoxia Exposure.Frontiers in physiology · 2021Review
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic intermittent hypoxia (CIH) and chronic hypoxia (CH) are associated with high-altitude pulmonary hypertension (HAPH). Asymmetric dimethylarginine (ADMA), a NO synthase (NOS) inhibitor, may contribute to HAPH. This study assessed changes in the ADMA/NO pathway and the underlying mechanisms in rat lungs following exposure to CIH or CH simulated in a hypobaric chamber at 428 Torr. Twenty-four adult Wistar rats were randomly assigned to three groups: CIH2x2 (2 days of hypoxia/2 days of normoxia), CH, and NX (permanent normoxia), for 30 days. All analyses were performed in whole lung tissue. L-Arginine and ADMA were analyzed using LC-MS/MS. Under both hypoxic conditions right ventricular hypertrophy was observed (p < 0.01) and endothelial NOS mRNA increased (p < 0.001), but the phosphorylated/nonphosphorylated vasodilator-stimulated phosphoprotein (VASP) ratio was unchanged. ADMA increased (p < 0.001), whereas dimethylarginine dimethylaminohydrolase (DDAH) activity decreased only under CH (p < 0.05). Although arginase activity increased (p < 0.001) and L-arginine exhibited no changes, the L-arginine/ADMA ratio decreased significantly (p < 0.001). Moreover, NOX4 expression increased only under CH (p < 0.01), but malondialdehyde (MDA) increased (up to 2-fold) equally in CIH2x2 and CH (p < 0.001). Our results suggest that ADMA and oxidative stress likely reduce NO bioavailability under altitude hypoxia, which implies greater pulmonary vascular reactivity and tone, despite the more subdued effects observed under CIH.
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