Oxidative-nitrosative stress and systemic vascular function in highlanders with and without exaggerated hypoxemia

Bailey, Damian M; Rimoldi, Stefano; Rexhaj, Emrush; Pratali, Lorenza; Salinas Salmòn, Carlos; Villena, Mercedes; McEneny, Jane; Young, Ian S; Nicod, Pascal; Allemann, Yves; Scherrer, Urs; Sartori, Claudio (2013). Oxidative-nitrosative stress and systemic vascular function in highlanders with and without exaggerated hypoxemia. Chest, 143(2), pp. 444-451. American College of Chest Physicians 10.1378/chest.12-0728

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology

UniBE Contributor:

Rimoldi, Stefano; Rexhaj, Emrush; Allemann, Yves; Scherrer, Urs and Sartori, Claudio

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0012-3692

Publisher:

American College of Chest Physicians

Language:

English

Submitter:

Stefano Rimoldi

Date Deposited:

03 Mar 2014 12:24

Last Modified:

13 Jul 2015 07:34

Publisher DOI:

10.1378/chest.12-0728

PubMed ID:

22922469

URI:

https://boris.unibe.ch/id/eprint/43131

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