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J Appl Physiol 92: 2501-2507, 2002. First published February 15, 2002; doi:10.1152/japplphysiol.00965.2001
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Vol. 92, Issue 6, 2501-2507, June 2002

Desferrioxamine elevates pulmonary vascular resistance in humans: potential for involvement of HIF-1

George M. Balanos, Keith L. Dorrington, and Peter A. Robbins

University Laboratory of Physiology, University of Oxford, Parks Road, Oxford OX1 3PT, United Kingdom

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.

hypoxia inducible factor-1; hypoxic pulmonary vasoconstriction; pulmonary circulation


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