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Intermittent hypobaric hypoxia induces oxidative stress and vascular remodeling in rat pulmonary arteries

Jurnal Medik Veteriner · Vol. 9 No. 1 (2026) · pp. 29–40

DOI
10.20473/jmv.vol9.iss1.2026.29-40
ISSN
2581-012X, 2615-7497
Published
2026-04-01
Publisher
Universitas Airlangga
Language
eng
License
creativecommons.org/licenses/by-nc-sa/4.0

Abstract

Flight crews frequently experience intermittent hypobaric hypoxia (IHH), which may trigger oxidative stress and vascular remodeling in the pulmonary arteries. This study investigated the effects of IHH exposure on oxidative stress markers, tunica media thickness, and the expression of LR11 and HIF-1α proteins in rat pulmonary arteries using five groups of healthy male Sprague–Dawley rats (n = 5 per group). Twenty-five male Sprague–Dawley rats were divided into five groups: a control group and four treatment groups exposed to simulated altitudes of 25,000 ft (7,620 m) for 5 minutes per day over 1, 3, 7, or 14 days. Levels of HIF-1α and LR11 were measured using ELISA, oxidative stress markers such as γ-glutamyl-cysteinyl-glycine (GSH) and malondialdehyde (MDA) were analyzed spectrophotometrically, and tunica media thickness was assessed histologically. HIF-1α levels peaked after acute hypoxia exposure and declined with prolonged exposure, whereas LR11 levels progressively increased, peaking in the 14-day group. MDA levels, reflecting oxidative stress, were highest after 3 days of exposure, while GSH levels decreased in all hypoxia groups compared with the control. Histological analysis showed the greatest tunica media thickness in the 3-day exposure group, followed by gradual reductions. Although no statistically significant correlations were found between protein levels and tunica media thickness, similar directional trends suggest biologically relevant associations. Intermittent hypobaric hypoxia (IHH) induces dynamic changes in oxidative stress and vascular remodeling in rat pulmonary arteries. Acute hypoxia increases HIF-1α expression and oxidative stress, whereas repeated exposures appear to trigger compensatory adaptations, including LR11 upregulation and tunica media remodeling. These findings demonstrate measurable molecular and structural alterations underlying pulmonary vascular responses to repeated high-altitude exposure.

Keywords

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29 authors · 82 co-authorship links

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Co-authorOrganisationJoint articles
Mohamad SadikinAffiliation unknown3
Sri Widia A. JusmanAffiliation unknown3
Margaretha HerawatiAffiliation unknown2
Fanny Septiani FarhanAffiliation unknown2
Frans FerdinalAffiliation unknown2
Nina OktarinaAffiliation unknown1
Mohammad KurniawanAffiliation unknown1
Yetty RamliAffiliation unknown1
Ahmad Sulaiman AlwahdyAffiliation unknown1
Berry JuliandiAffiliation unknown1
Yayi Dwina Bilianti SusantoAffiliation unknown1
Wardaya WardayaAffiliation unknown1
Ani Retno PrijantiAffiliation unknown1
Abdul Halim SadikinAffiliation unknown1
Sri Widia Azraki JusmanAffiliation unknown1
Siti NurkasanahAffiliation unknown1
Aida S.D. HoemardaniAffiliation unknown1
Evlina Suzanna SinurayaAffiliation unknown1
Dwi Anita SuryandariAffiliation unknown1
Yuda Nabella PrameswariAffiliation unknown1
Luluk YunainiAffiliation unknown1
Ria KodariahAffiliation unknown1

Affiliations come from OpenAlex; journal OAI-PMH metadata carries none. Authors without an OpenAlex ID are matched by name, which can merge or split people.

Metadata source: OAI-PMH (metadata jurnal) https://e-journal.unair.ac.id/JMV/oai, first harvested 9 Nov 2026, last seen 9 Nov 2026.
Original metadata (oai_dc)
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	<dc:title xml:lang="en-US">Intermittent hypobaric hypoxia induces oxidative stress and vascular remodeling in rat pulmonary arteries</dc:title>
	<dc:creator>Ardi, Sri Nurbowo</dc:creator>
	<dc:creator>Putra, Muhammad Arza</dc:creator>
	<dc:creator>Sukmawati, Dewi</dc:creator>
	<dc:creator>Wuyung, Puspita Eka</dc:creator>
	<dc:creator>Mulyawan, Wawan</dc:creator>
	<dc:creator>Wardaya</dc:creator>
	<dc:creator>Wiyono, Wiwien Heru</dc:creator>
	<dc:subject xml:lang="en-US">hypobaric hypoxia</dc:subject>
	<dc:subject xml:lang="en-US">oxidative stress</dc:subject>
	<dc:subject xml:lang="en-US">tunica media</dc:subject>
	<dc:subject xml:lang="en-US">LR11</dc:subject>
	<dc:subject xml:lang="en-US">HIF-1α</dc:subject>
	<dc:description xml:lang="en-US">Flight crews frequently experience intermittent hypobaric hypoxia (IHH), which may trigger oxidative stress and vascular remodeling in the pulmonary arteries. This study investigated the effects of IHH exposure on oxidative stress markers, tunica media thickness, and the expression of LR11 and HIF-1α proteins in rat pulmonary arteries using five groups of healthy male Sprague–Dawley rats (n = 5 per group). Twenty-five male Sprague–Dawley rats were divided into five groups: a control group and four treatment groups exposed to simulated altitudes of 25,000 ft (7,620 m) for 5 minutes per day over 1, 3, 7, or 14 days. Levels of HIF-1α and LR11 were measured using ELISA, oxidative stress markers such as γ-glutamyl-cysteinyl-glycine (GSH) and malondialdehyde (MDA) were analyzed spectrophotometrically, and tunica media thickness was assessed histologically. HIF-1α levels peaked after acute hypoxia exposure and declined with prolonged exposure, whereas LR11 levels progressively increased, peaking in the 14-day group. MDA levels, reflecting oxidative stress, were highest after 3 days of exposure, while GSH levels decreased in all hypoxia groups compared with the control. Histological analysis showed the greatest tunica media thickness in the 3-day exposure group, followed by gradual reductions. Although no statistically significant correlations were found between protein levels and tunica media thickness, similar directional trends suggest biologically relevant associations. Intermittent hypobaric hypoxia (IHH) induces dynamic changes in oxidative stress and vascular remodeling in rat pulmonary arteries. Acute hypoxia increases HIF-1α expression and oxidative stress, whereas repeated exposures appear to trigger compensatory adaptations, including LR11 upregulation and tunica media remodeling. These findings demonstrate measurable molecular and structural alterations underlying pulmonary vascular responses to repeated high-altitude exposure.</dc:description>
	<dc:publisher xml:lang="en-US">Universitas Airlangga</dc:publisher>
	<dc:date>2026-04-01</dc:date>
	<dc:type>info:eu-repo/semantics/article</dc:type>
	<dc:type>info:eu-repo/semantics/publishedVersion</dc:type>
	<dc:format>application/pdf</dc:format>
	<dc:format>text/xml</dc:format>
	<dc:identifier>https://e-journal.unair.ac.id/JMV/article/view/77492</dc:identifier>
	<dc:identifier>10.20473/jmv.vol9.iss1.2026.29-40</dc:identifier>
	<dc:source xml:lang="en-US">Jurnal Medik Veteriner; Vol. 9 No. 1 (2026): April; 29-40</dc:source>
	<dc:source>2581-012X</dc:source>
	<dc:source>2615-7497</dc:source>
	<dc:language>eng</dc:language>
	<dc:relation>https://e-journal.unair.ac.id/JMV/article/view/77492/36885</dc:relation>
	<dc:relation>https://e-journal.unair.ac.id/JMV/article/view/77492/37700</dc:relation>
	<dc:rights xml:lang="en-US">Copyright (c) 2026 Sri Nurbowo Ardi, Muhammad Arza Putra, Dewi Sukmawati, Puspita Eka Wuyung, Wawan Mulyawan, Wardaya, Wiwien Heru Wiyono</dc:rights>
	<dc:rights xml:lang="en-US">http://creativecommons.org/licenses/by-nc-sa/4.0</dc:rights>
</oai_dc:dc>