Abstract
Hypoxic exposure over several days leads to a progressive decline in plasma volume (PV). The resulting hemoconcentration restores the initially reduced arterial O2 content to normal or higher levels. Atrial natriuretic peptide (ANP) with its natriuretic and diuretic action may be involved in the regulation of this process. Indeed, both animal and human studies have reported that acute hypoxia augments ANP potentially by a direct effect on the atrial myocyte and/or by facilitating pulmonary vasoconstriction that increases the afterload and hence the distension of the right heart. In contrast to this acute effect, a reduction in ANP is commonly observed after prolonged (2-7 days) hypoxic exposure and the mechanism underlying this reduction is unclear. In this study, we tested whether the reduced O2 tension or the PV contraction, which reduces cardiac preload and hence atrial wall stretch, are involved. Eleven healthy males completed a 4 day hypoxia sojourn (3,500m) in a fully controlled (i.e., exercise, food and fluid intake) hypobaric chamber setting. PV was determined before and in the end of the sojourn by CO rebreathing. Venous concentrations of MR-ProANP, a stable marker for ANP, were measured before and on the last morning of the sojourn. On the last morning, further measurements were performed after breathing a hyperoxic gas mixture (30 min) that normalized arterial O2 tension as well as after restoration of PV to baseline values by infusion of a crystalloid solution. Four days exposure to 3,500 m reduced MR-ProANP from 39.4±16.0 to 25.9±10.8 pmol/L, (p=0.019). MR-ProANP remained unchanged after administration of O2 (25.4±11.8 pmol/L, p=0.774), but increased (p=0.042) with PV restoration to 33.2±17.7 pmol/L (p=0.307 vs. baseline). These findings support that plasma volume contraction, at least partially, explains the ANP reduction at altitude, whereas the reduced arterial oxygen tension does not seem to contribute.