Hypoxia and vascular nitric oxide bioavailability: Hypoximplications for the pathophysiology of high-altitude illness
type: CreativeWork
description: Introduction: Nitric oxide (NO) is an integral molecule implicated in the control of vascular function. It has been suggested that vascular dysfunction may lead to the development of acute mountain sickness (AMS), high-altitude cerebral oedema (HACE) and high-altitude pulmonary oedema (HAPE), though data to date remains scarce. Therefore, there is a clear need for further work to address the role of NO in the pathogenesis of high-altitude illness.Aims: There were two primary aims of the current work: (1) To examine whether hypoxia mediated changes in systemic NO metabolism are related to the development of AMS andsub-clinical pulmonary oedema and (2) to examine whether hypoxia mediated changes in the trans-cerebral exchange kinetics of NO metabolites are related to the development of AMSand headache.Hypothesis: We hypothesise that hypoxia will be associated with an increase in reactive oxygen species (ROS) formation, resulting in a decrease in vascular NO bioavailability (O2•-+ NO → ONOO•-, k = 109 M.s-1). The reduction in NO will lead to vascular dysfunction and impaired oxygen (O2) delivery. Subsequent hypoxaemia will result in pulmonary vascularvasoconstriction and the development of sub-clinical pulmonary oedema within and mild brain swelling. Symptoms and reductions in NO bioavailability will be more pronounced in those who develop AMS since they are typically more hypoxaemic. Alternatively, a hypoxia mediated increase in NO, during vasodilatation, specifically across the cerebral circulation,may activate the trigminovascular system resulting in headache and by consequence, AMS.Methods: Study 1 – AMS symptoms, systemic venous NO concentration and nasal potential difference (NPD), used as a surrogate biomarker of extravascular lung oedema, werequantified in normoxia, after a 6hr passive exposure to 12% oxygen (O2) and immediately following a hypoxic maximal exercise challenge (≈6.5 hrs). Final measurements were 2 obtained two hours into (hypoxic) recovery. Study…
abstract: Introduction: Nitric oxide (NO) is an integral molecule implicated in the control of vascular function. It has been suggested that vascular dysfunction may lead to the development of acute mountain sickness (AMS), high-altitude cerebral oedema (HACE) and high-altitude pulmonary oedema (HAPE), though data to date remains scarce. Therefore, there is a clear need for further work to address the role of NO in the pathogenesis of high-altitude illness.Aims: There were two primary aims of the current work: (1) To examine whether hypoxia mediated changes in systemic NO metabolism are related to the development of AMS andsub-clinical pulmonary oedema and (2) to examine whether hypoxia mediated changes in the trans-cerebral exchange kinetics of NO metabolites are related to the development of AMSand headache.Hypothesis: We hypothesise that hypoxia will be associated with an increase in reactive oxygen species (ROS) formation, resulting in a decrease in vascular NO bioavailability (O2•-+ NO → ONOO•-, k = 109 M.s-1). The reduction in NO will lead to vascular dysfunction and impaired oxygen (O2) delivery. Subsequent hypoxaemia will result in pulmonary vascularvasoconstriction and the development of sub-clinical pulmonary oedema within and mild brain swelling. Symptoms and reductions in NO bioavailability will be more pronounced in those who develop AMS since they are typically more hypoxaemic. Alternatively, a hypoxia mediated increase in NO, during vasodilatation, specifically across the cerebral circulation,may activate the trigminovascular system resulting in headache and by consequence, AMS.Methods: Study 1 – AMS symptoms, systemic venous NO concentration and nasal potential difference (NPD), used as a surrogate biomarker of extravascular lung oedema, werequantified in normoxia, after a 6hr passive exposure to 12% oxygen (O2) and immediately following a hypoxic maximal exercise challenge (≈6.5 hrs). Final measurements were 2 obtained two hours into (hypoxic) recovery. Study…
author: Evans, Kevin Andrew
language: eng
keywords: Hypoxia, high-altitude illness, acute mountain sickness, AMS, high-altitude cerebral oedema, HACE, Nitric Oxide
date published: 2009-12
date modified: 2026-07-24T04:38:39Z
provider: University of South Wales
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of South Wales