Damian M Bailey1, Stefano F Rimoldi2, Emrush Rexhaj2, Lorenza Pratali3, Carlos Salinas Salmòn4, Mercedes Villena4, Jane McEneny5, Ian S Young5, Pascal Nicod6, Yves Allemann2, Urs Scherrer7, Claudio Sartori8. 1. Neurovascular Research Laboratory, Faculty of Health, Science and Sport, University of Glamorgan, Wales; Sondes Moléculaires en Biologie et Stress Oxydant, Institut de Chimie Radicalaire, Centre National de la Recherche Scientifique UMR 7273, Aix-Marseille University, France. Electronic address: dbailey1@glam.ac.uk. 2. Department of Cardiology, University Hospital of Bern, Bern, Switzerland. 3. Institute of Clinical Physiology, CNR, Pisa, Italy. 4. Instituto Boliviano de Biologia de Altura, La Paz, Bolivia. 5. Centre for Clinical and Population Sciences, Queen's University Belfast, Belfast, Northern Ireland. 6. Botnar Center for Clinical Research, Hirslanden Group, Lausanne, Switzerland. 7. Department of Cardiology, University Hospital of Bern, Bern, Switzerland; Botnar Center for Clinical Research, Hirslanden Group, Lausanne, Switzerland; Facultad de Ciencias, Departamento de Biología, Universidad de Tarapacá, Arica, Chile. 8. Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Abstract
BACKGROUND: Acute exposure to high altitude stimulates free radical formation in lowlanders, yet whether this persists during chronic exposure in healthy, well-adapted and maladapted highlanders suffering from chronic mountain sickness (CMS) remains to be established. METHODS: Oxidative-nitrosative stress (as determined by the presence of the biomarkers ascorbate radical [A •- ], via electron paramagnetic resonance spectroscopy, and nitrite [NO 2 2 ], via ozone-based chemiluminescence) was assessed in venous blood of 25 male highlanders in Bolivia living at 3,600 m with CMS (n 5 13, CMS 1 ) and without CMS (n 5 12, CMS 2 ). Twelve age- and activity-matched, healthy, male lowlanders were examined at sea level and during acute hypoxia. We also measured fl ow-mediated dilatation (FMD), arterial stiffness defined by augmentation index normalized for a heart rate of 75 beats/min (AIx-75), and carotid intima-media thickness (IMT). RESULTS: Compared with normoxic lowlanders, oxidative-nitrosative stress was moderately increased in the CMS 2 group ( P , .05), as indicated by elevated A •- (3,191 457 arbitrary units [AU] vs 2,640 445 AU) and lower NO 2 2 (206 55 nM vs 420 128 nM), whereas vascular function remained preserved. This was comparable to that observed during acute hypoxia in lowlanders in whom vascular dysfunction is typically observed. In contrast, this response was markedly exaggerated in CMS 1 group (A •- , 3,765 429 AU; NO 2 2 , 148 50 nM) compared with both the CMS 2 group and lowlanders ( P , .05). This was associated with systemic vascular dysfunction as indicated by lower ( P , .05 vs CMS 2 ) FMD (4.2% 0.7% vs 7.6% 1.7%) and increased AIx-75 (23% 8% vs 12% 7%) and carotid IMT (714 127 m M vs 588 94 m M). CONCLUSIONS: Healthy highlanders display a moderate, sustained elevation in oxidative-nitrosative stress that, unlike the equivalent increase evoked by acute hypoxia in healthy lowlanders, failed to affect vascular function. Its more marked elevation in patients with CMS may contribute to systemic vascular dysfunction.
BACKGROUND: Acute exposure to high altitude stimulates free radical formation in lowlanders, yet whether this persists during chronic exposure in healthy, well-adapted and maladapted highlanders suffering from chronic mountain sickness (CMS) remains to be established. METHODS: Oxidative-nitrosative stress (as determined by the presence of the biomarkers ascorbate radical [A •- ], via electron paramagnetic resonance spectroscopy, and nitrite [NO 2 2 ], via ozone-based chemiluminescence) was assessed in venous blood of 25 male highlanders in Bolivia living at 3,600 m with CMS (n 5 13, CMS 1 ) and without CMS (n 5 12, CMS 2 ). Twelve age- and activity-matched, healthy, male lowlanders were examined at sea level and during acute hypoxia. We also measured fl ow-mediated dilatation (FMD), arterial stiffness defined by augmentation index normalized for a heart rate of 75 beats/min (AIx-75), and carotid intima-media thickness (IMT). RESULTS: Compared with normoxic lowlanders, oxidative-nitrosative stress was moderately increased in the CMS 2 group ( P , .05), as indicated by elevated A •- (3,191 457 arbitrary units [AU] vs 2,640 445 AU) and lower NO 2 2 (206 55 nM vs 420 128 nM), whereas vascular function remained preserved. This was comparable to that observed during acute hypoxia in lowlanders in whom vascular dysfunction is typically observed. In contrast, this response was markedly exaggerated in CMS 1 group (A •- , 3,765 429 AU; NO 2 2 , 148 50 nM) compared with both the CMS 2 group and lowlanders ( P , .05). This was associated with systemic vascular dysfunction as indicated by lower ( P , .05 vs CMS 2 ) FMD (4.2% 0.7% vs 7.6% 1.7%) and increased AIx-75 (23% 8% vs 12% 7%) and carotid IMT (714 127 m M vs 588 94 m M). CONCLUSIONS: Healthy highlanders display a moderate, sustained elevation in oxidative-nitrosative stress that, unlike the equivalent increase evoked by acute hypoxia in healthy lowlanders, failed to affect vascular function. Its more marked elevation in patients with CMS may contribute to systemic vascular dysfunction.
Authors: Takuro Washio; Benjamin S Stacey; Shigehiko Ogoh; Hayato Tsukamoto; Angelo Iannetelli; Thomas S Owens; Thomas A Calverley; Lewis Fall; Christopher J Marley; Damian M Bailey Journal: J Physiol Sci Date: 2022-07-20 Impact factor: 2.257
Authors: Nia C S Lewis; Damian M Bailey; Gregory R Dumanoir; Laura Messinger; Samuel J E Lucas; James D Cotter; Joseph Donnelly; Jane McEneny; Ian S Young; Mike Stembridge; Keith R Burgess; Aparna S Basnet; Philip N Ainslie Journal: J Physiol Date: 2013-12-09 Impact factor: 5.182
Authors: Michael M Tymko; Justin S Lawley; Philip N Ainslie; Alexander B Hansen; Florian Hofstaetter; Simon Rainer; Sachin Amin; Gilbert Moralez; Christopher Gasho; Gustavo Vizcardo-Galindo; Daniela Bermudez; Francisco C Villafuerte; Christopher M Hearon Journal: Circ Res Date: 2020-04-09 Impact factor: 17.367
Authors: Ryan L Hoiland; Anthony R Bain; Mathew G Rieger; Damian M Bailey; Philip N Ainslie Journal: Am J Physiol Regul Integr Comp Physiol Date: 2015-12-16 Impact factor: 3.619
Authors: Aldo De Ferrari; J Jaime Miranda; Robert H Gilman; Victor G Dávila-Román; Fabiola León-Velarde; Maria Rivera-Ch; Luis Huicho; Antonio Bernabé-Ortiz; Robert A Wise; William Checkley Journal: Chest Date: 2014-11 Impact factor: 9.410