Hypoxia briefly increases diuresis but reduces plasma volume by fluid redistribution in women

Johanna Roche, Peter Rasmussen, Hannes Gatterer, Giulia Roveri, Rachel Turner, Gerrit van Hall, Marc Maillard, Anna Walzl, Michael Kob, Giacomo Strapazzon, Jens Peter Goetze, Simon Thomas Schäfer, Tobias Kammerer, Elie Nader, Philippe Connes, Mélanie Robert, Thomas Mueller, Eric Feraille, Christoph Siebenmann*

*Corresponding author for this work

Abstract

We have recently reported that hypobaric hypoxia (HH) reduces plasma volume (PV) in men by decreasing total circulating plasma protein (TCPP). Here, we investigated whether this applies to women and whether an inflammatory response and/or endothelial glycocalyx shedding could facilitate the TCCP reduction. We further investigated whether acute HH induces a short-lived diuretic response that was overlooked in our recent study, where only 24-h urine volumes were evaluated. In a strictly controlled crossover protocol, 12 women underwent two 4-day sojourns in a hypobaric chamber: one in normoxia (NX) and one in HH equivalent to 3,500-m altitude. PV, urine output, TCPP, and markers for inflammation and glycocalyx shedding were repeatedly measured. Total body water (TBW) was determined pre- and postsojourns by deuterium dilution. PV was reduced after 12 h of HH and thereafter remained 230-330 mL lower than in NX (P < 0.0001). Urine flow was 45% higher in HH than in NX throughout the first 6 h (P = 0.01) but lower during the second half of the first day (P < 0.001). Twenty-four-hour urine volumes (P ≥ 0.37) and TBW (P ≥ 0.14) were not different between the sojourns. TCPP was lower in HH than in NX at the same time points as PV (P < 0.001), but inflammatory or glycocalyx shedding markers were not consistently increased. As in men, and despite initially increased diuresis, HH-induced PV contraction in women is driven by a loss of TCPP and ensuing fluid redistribution, rather than by fluid loss. The mechanism underlying the TCPP reduction remains unclear but does not seem to involve inflammation or glycocalyx shedding.NEW & NOTEWORTHY This study is the first to investigate the mechanisms underlying plasma volume (PV) contraction in response to hypoxia in women while strictly controlling for confounders. PV contraction in women has a similar time course and magnitude as in men and is driven by the same mechanism, namely, oncotically driven redistribution rather than loss of fluid. We further report that hypoxia facilitates an increase in diuresis, that is, however, short-lived and of little relevance for PV regulation.

Original languageEnglish
JournalAmerican Journal of Physiology: Heart and Circulatory Physiology
Volume323
Issue number6
Pages (from-to)H1068-H1079
ISSN0363-6135
DOIs
Publication statusPublished - 1 Dec 2022

Keywords

  • Male
  • Humans
  • Female
  • Plasma Volume/physiology
  • Hypoxia
  • Altitude
  • Diuresis
  • Inflammation

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