ArticlePhysiological reports2014
Contrasting effects of ascorbate and iron on the pulmonary vascular response to hypoxia in humans.
Article in Physiological reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Intravenous iron delivers a sustained (8-week) lowering of pulmonary artery pressure during exercise in healthy older humans.Physiological reports · 2019Trial
- Human hypoxic pulmonary vasoconstriction is unaltered by 8 h of preceding isocapnic hyperoxia.Physiological reports · 2017Trial
- Elevation of iron storage in humans attenuates the pulmonary vascular response to hypoxia.Journal of applied physiology (Bethesda, Md. : 1985) · 2016Trial
- Iron and the lung: emerging roles of iron metabolism in pulmonary disease pathogenesis and therapy.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- HIF-2α could be a key regulator of Fe homeostasis in the gut of yellow-feathered broilers.Poultry science · 2026Article
- Oxygen-sensing pathways and the pulmonary circulation.The Journal of physiology · 2024Review
- Iron deficiency and supplementation in heart failure.Nature reviews. Cardiology · 2024Review
- Hypoxic pulmonary vasoconstriction does not limit maximal exercise capacity in healthy volunteers breathing 12% oxygen at sea level.Physiological reports · 2024Article
- Abnormal whole-body energy metabolism in iron-deficient humans despite preserved skeletal muscle oxidative phosphorylation.Scientific reports · 2022Article
- Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders.International journal of environmental research and public health · 2021Review
- Iron deficiency is a possible risk factor causing right heart failure in Tibetan children living in high altitude area.Medicine · 2020Article
- Metabolism and Redox in Pulmonary Vascular Physiology and Pathophysiology.Antioxidants & redox signaling · 2019Review
- Vitamin C: the known and the unknown and Goldilocks.Oral diseases · 2016Review
- Clinical iron deficiency disturbs normal human responses to hypoxia.The Journal of clinical investigation · 2016Observational
- Iron, oxygen, and the pulmonary circulation.Journal of applied physiology (Bethesda, Md. : 1985) · 2015Review
- The Role of Oxygen Sensors, Hydroxylases, and HIF in Cardiac Function and Disease.Oxidative medicine and cellular longevity · 2015Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Hypoxia causes an increase in pulmonary artery pressure. Gene expression controlled by the hypoxia-inducible factor (HIF) family of transcription factors plays an important role in the underlying pulmonary vascular responses. The hydroxylase enzymes that regulate HIF are highly sensitive to varying iron availability, and iron status modifies the pulmonary vascular response to hypoxia, possibly through its effects on HIF. Ascorbate (vitamin C) affects HIF hydroxylation in a similar manner to iron and may therefore have similar pulmonary effects. This study investigated the possible contribution of ascorbate availability to hypoxic pulmonary vasoconstriction in humans. Seven healthy volunteers undertook a randomized, controlled, double-blind, crossover protocol which studied the effects of high-dose intravenous ascorbic acid (total 6 g) on the pulmonary vascular response to 5 h of sustained hypoxia. Systolic pulmonary artery pressure (SPAP) was assessed during hypoxia by Doppler echocardiography. Results were compared with corresponding data from a similar study investigating the effect of intravenous iron, in which SPAP was measured in seven healthy volunteers during 8 h of sustained hypoxia. Consistent with other studies, iron supplementation profoundly inhibited hypoxic pulmonary vasoconstriction (P < 0.001). In contrast, supraphysiological supplementation of ascorbate did not affect the increase in pulmonary artery pressure induced by several hours of hypoxia (P = 0.61). We conclude that ascorbate does not interact with hypoxia and the pulmonary circulation in the same manner as iron. Whether the effects of iron are HIF-mediated remains unknown, and the extent to which ascorbate contributes to HIF hydroxylation in vivo is also unclear.
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