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Effects of altitude exposure on brain natriuretic peptide in humans

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Abstract

Acute mountain sickness (AMS) is common at high altitude (HA) and associated with a relative failure of the natriuresis and diuresis that occurs at HA. The role of Brain Natriuretic Peptide (BNP) in this context has not been thoroughly investigated. We aimed to clarify if BNP rises in response to exercise at HA and if so whether this is related to AMS. 32 healthy subjects had assessments of BNP, aldosterone and AMS scores [as assessed by the AMS-C score of the Environmental Symptom Questionnaire (ESQ) and Lake Louise questionnaire] made following exertion at sea-level (SL), 3,400, 4,300 and 5,150 m. Data were analysed in the 23 subjects who did not consume drugs known to affect acclimatization. BNP (pg/ml, mean ± SEM) was significantly higher at 5,150 m versus the lower altitudes (p < 0.001 for all): 7.1 ± 1; 6.1 ± 0.3; 6.8 ± 0.9 and 17.7 ± 5.1 at sea-level; 3,400, 4,300 and 5,150 m. In those that showed a BNP response at 5,150 m (n = 19) versus those that did not demonstrate a BNP response (n = 4) there was a significant difference in Lake Louise (LL) AMS scores at 5,150 m on day 10 of the expedition (mean LL score 3.3 vs. 0.75, p = 0.034) and day 11 (mean LL score 3.3 vs. 0, p = 0.003). This is the first report to demonstrate a significant rise in BNP at HA. A BNP response at 5,150 m may be associated with a greater likelihood of suffering AMS.

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References

  • Ainslie PN, Ogoh S, Burgess K, Celi L, McGrattan K, Peebles K, Murrell C, Subedi P, Burgess KR (2008) Differential effects of acute hypoxia and high altitude on cerebral blood flow velocity and dynamic cerebral autoregulation: alterations with hyperoxia. J Appl Physiol 104:490–498

    Article  PubMed  Google Scholar 

  • Balion CM, Santaguida P, McKelvie R, Hill SA, McQueen MJ, Worster A, Raina PS (2008) Physiological, pathological, pharmacological, biochemical and hematological factors affecting BNP and NT-proBNP. Clin Biochem 41:231–239

    Article  PubMed  CAS  Google Scholar 

  • Bartsch P, Maggiorini M, Schobersberger W, Shaw S, Rascher W, Girard J, Weidmann P, Oelz O (1991a) Enhanced exercise-induced rise of aldosterone and vasopressin preceding mountain sickness. J Appl Physiol 71:136–143

    PubMed  CAS  Google Scholar 

  • Bartsch P, Pfluger N, Audetat M, Shaw S, Weidmann P, Vock P, Vetter W, Rennie D, Oelz O (1991b) Effects of slow ascent to 4559 m on fluid homeostasis. Aviat Space Environ Med 62:105–110

    PubMed  CAS  Google Scholar 

  • Bernheim AM, Kiencke S, Fischler M, Dorschner L, Debrunner J, Mairbäurl H, Maggiorini M, Brunner-La Rocca HP (2007) Acute changes in pulmonary artery pressures due to exercise and exposure to high altitude do not cause left ventricular diastolic dysfunction. Chest 132:380–387

    Article  PubMed  Google Scholar 

  • Cargill RI, McFarlane LC, Coutie WJ, Lipworth BJ (1996) Acute neurohormonal responses to hypoxaemia in man. Eur J Appl Physiol 72:256–260

    Article  CAS  Google Scholar 

  • Casals G, Ros J, Sionis A, Davidson MM, Morales-Ruiz M, Jiménez W (2009) Hypoxia induces B-type natriuretic peptide release in cell lines derived from human cardiomyocytes. Am J Physiol Heart Circ Physiol 297:H550–H555

    Article  PubMed  CAS  Google Scholar 

  • Dean AG, Yip R, Hoffmann RE (1990) High incidence of mild acute mountain sickness in conference attendees at 10,000 ft altitude. J Wilderness Med 1:86–92

    Article  Google Scholar 

  • Due-Andersen R, Pedersen-Bjergaard U, Høi-Hansen T, Olsen NV, Kistorp C, Faber J, Boomsma F, Thorsteinsson B (2008) NT-pro-BNP during hypoglycemia and hypoxemia in normal subjects: impact of renin-angiotensin system activity. J Appl Physiol 104:1080–1085

    Article  PubMed  CAS  Google Scholar 

  • Feddersen B, Ausserer H, Haditsch B, Frisch H, Noachtar S, Straube A (2009) Brain natriuretic peptide at altitude: relationship to diuresis, natriuresis, and mountain sickness. Aviat Space Environ Med 80:108–111

    Article  PubMed  CAS  Google Scholar 

  • Fragasso G, Palloshi A, Roi S, Rossetti E, Monaco G, Dolci A, Margonato A, Chierchia S (2004) Transient cardiac left ventricular diastolic dysfunction following strenuous exercise. Sport Sci Health 1:31–35

    Article  Google Scholar 

  • Fulco CS, Hoyt RW, Baker-Fulco CJ, Gonzales J, Cymerman A (1992) Use of bioelectrical impedance to assess body composition changes at high altitude. J Appl Physiol 72:2181–2187

    PubMed  CAS  Google Scholar 

  • Goto K, Arai M, Watanabe A, Hasegawa A, Nakano A, Kurabayashi M (2010) Utility of echocardiography versus BNP level for the prediction of pulmonary arterial pressure in patients with pulmonary arterial hypertension. Int Heart J 51:343–347

    Article  PubMed  Google Scholar 

  • Hackett PH, Oelz O (1992) The Lake Louise consensus on the quantification of altitude illness. In: Sutton JR, Houston CS, Coates G (eds) Mountain medicine hypoxia. Queen City Printers, Burlington, pp 327–330

    Google Scholar 

  • Hackett PH, Rennie D, Hofmeister SE, Grover RF, Grover EB, Reeves JT (1982) Fluid retention and relative hypoventilation in acute mountain sickness. Respiration 43:321–329

    Article  PubMed  CAS  Google Scholar 

  • Hall C (2005) NT-ProBNP: the mechanism behind the marker. J Card Fail 11:S81–S83

    Article  PubMed  CAS  Google Scholar 

  • Hew-Butler T, Noakes TD, Soldin SJ, Verbalis JG (2008) Acute changes in endocrine and fluid balance markers during high-intensity, steady-state, and prolonged endurance running: unexpected increases in oxytocin and brain natriuretic peptide during exercise. Eur J Endocrinol 159:729–737

    Article  PubMed  CAS  Google Scholar 

  • Kamimori GH, Ryan EJ, Otterstetter R, Barkley JE, Glickman EL, Davis HQ (2009) Catecholamine levels in hypoxia-induced acute mountain sickness. Aviat Space Environ Med 80:376–380

    Article  PubMed  CAS  Google Scholar 

  • Kjaergaard J, Snyder EM, Hassager C, Olson TP, Oh JK, Johnson BD (2006) The effect of 18 h of simulated high altitude on left ventricular function. Eur J Appl Physiol 98:411–418

    Article  PubMed  Google Scholar 

  • Lubien E, DeMaria A, Krishnaswamy P, Clopton P, Koon J, Kazanegra R, Gardetto N, Wanner E, Maisel AS (2002) Utility of B-natriuretic peptide in detecting diastolic dysfunction: comparison with Doppler velocity recordings. Circulation 105:595–601

    Article  PubMed  CAS  Google Scholar 

  • Maggiorini M, Buhler B, Walter M, Oelz O (1990) Prevalence of acute mountain sickness in the Swiss Alps. BMJ 301:853–855

    Article  PubMed  CAS  Google Scholar 

  • Marumoto K, Hamada M, Hiwada K (1995) Increased secretion of atrial and brain natriuretic peptides during acute myocardial ischaemia induced by dynamic exercise in patients with angina pectoris. Clin Sci Colch 88:551–556

    PubMed  CAS  Google Scholar 

  • Milledge JS, Catley DM, Williams ES, Withey WR, Minty BD (1983) Effect of prolonged exercise at altitude on the renin-aldosterone system. J Appl Physiol 55:413–418

    PubMed  CAS  Google Scholar 

  • Nakanishi K, Tajima F, Itoh H, Nakata Y, Osada H, Hama N, Nakagawa O, Nakao K, Kawai T, Takishima K, Aurues T, Ikeda T (2001) Changes in atrial natriuretic peptide and brain natriuretic peptide associated with hypobaric hypoxia-induced pulmonary hypertension in rats. Virchows Arch 439:808–817

    PubMed  CAS  Google Scholar 

  • Nicholson S, Richards M, Espiner E, Nicholls G, Yandle T (1993) Atrial and brain natriuretic peptide response to exercise in patients with ischaemic heart disease. Clin Exp Pharmacol Physiol 20:535–540

    Article  PubMed  CAS  Google Scholar 

  • Nishikimi T, Morimoto A, Ishikawa K, Saito Y, Kangawa K, Matsuo H, Kitamura K, Takishita S, Matsuoka H (1997) Different secretion patterns of adrenomedullin, brain natriuretic peptide, and atrial natriuretic peptide during exercise in hypertensive and normotensive subjects. Clin Exp Hypertens 19:503–518

    Article  PubMed  CAS  Google Scholar 

  • Sampson JB, Cymerman A, Burse RL, Maher JT, Rock PB (1983) Procedures for the measurement of acute mountain sickness. Aviat Space Environ Med 54:1063–1073

    PubMed  CAS  Google Scholar 

  • Scharhag J, Herrmann M, Urhausen A, Haschke M, Herrmann W, Kindermann W (2005) Independent elevations of N-terminal pro-brain natriuretic peptide and cardiac troponins in endurance athletes after prolonged strenuous exercise. Am Heart J 150:1128–1134

    Article  PubMed  CAS  Google Scholar 

  • Scharhag J, Meyer T, Auracher M, Müller M, Herrmann M, Gabriel H, Herrmann W, Kindermann W (2008) Exercise-induced increases in NT-proBNP are not related to the exercise-induced immune response. Br J Sports Med 42:383–385

    Article  PubMed  CAS  Google Scholar 

  • Shah MB, Braude D, Crandall CS, Kwack H, Rabinowitz L, Cumbo TA, Basnyat B, Bhasyal G (2006) Changes in metabolic and hematologic laboratory values with ascent to altitude and the development of acute mountain sickness in Nepalese pilgrims. Wild Environ Med 17:171–177

    Article  Google Scholar 

  • Toshner MR, Thompson AAR, Irving JB, Baillie JK, Morton JJ, Peacock AJ (2008) NT-proBNP does not rise on acute ascent to high altitude. High Alt Med Biol 9:1–4

    Article  Google Scholar 

  • Weidemann A, Klanke B, Wagner M, Volk T, Willam C, Wiesener MS, Eckardt KU, Warnecke C (2008) Hypoxia, via stabilization of the hypoxia-inducible factor HIF-1alpha, is a direct and sufficient stimulus for brain-type natriuretic peptide induction. Biochem J 409:233–242

    Article  PubMed  CAS  Google Scholar 

  • Zaccaria M, Rocco S, Noventa D, Varnier M, Opocher G (1998) Sodium regulating hormones at high altitude: basal and post–exercise levels. J Clin Endocrinol Metab 83:570–574

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We would like to thank all members of the Exercise Imja Tse team from the Defence Medical Services. This research was supported by The Drummond Foundation. And many thanks to The Research Department of the Faculty of Health, Birmingham City University for contributing to the costs of the expedition and Inverness Medical (Alere), UK Ltd for the unconditional loan of the Biosite Triage machines.

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There are no potential conflicts of interest to declare for any of the authors.

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Correspondence to David Woods.

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Communicated by Guido Ferretti.

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Woods, D., Hooper, T., Hodkinson, P. et al. Effects of altitude exposure on brain natriuretic peptide in humans. Eur J Appl Physiol 111, 2687–2693 (2011). https://doi.org/10.1007/s00421-011-1881-8

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  • DOI: https://doi.org/10.1007/s00421-011-1881-8

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