Affiliation:
1. University Laboratory of Physiology, University of Oxford, Parks Road, Oxford OX1 3PT, United Kingdom
Abstract
Hypoxia-inducible factor (HIF)-1 is stabilized by hypoxia and iron chelation. We hypothesized that HIF-1 might be involved in pulmonary vascular regulation and that infusion of desferrioxamine over 8 h would consequently mimic hypoxia and elevate pulmonary vascular resistance. In study A, we characterized the pulmonary vascular response to 4 h of isocapnic hypoxia; in study B, we measured the pulmonary vascular response to 8 h of desferrioxamine infusion. For study A, 11 volunteers undertook two protocols: 1) 4 h of isocapnic hypoxia (end-tidal Po2= 50 Torr), followed by 2 h of recovery with isocapnic euoxia (end-tidal Po2= 100 Torr), and 2) 6 h of air breathing (control). For study B, nine volunteers undertook two protocols while breathing air: 1) continuous infusion of desferrioxamine (4 g/70 kg) over 8 h and 2) continuous infusion of saline over 8 h (control). In both studies, pulmonary vascular resistance was assessed at 0.5- to 1-h intervals by Doppler echocardiography via the maximum pressure gradient during systole across the tricuspid valve. Results show a progressive rise in pressure gradient over the first 3–4 h with both isocapnic hypoxia ( P < 0.001) and desferrioxamine infusion ( P < 0.005) to increases of ∼16 and 4 Torr, respectively. These results support a role for HIF-regulated gene activation in human hypoxic pulmonary vasoconstriction.
Publisher
American Physiological Society
Subject
Physiology (medical),Physiology
Cited by
59 articles.
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