Kechun Tang (a), Ellen C. Breen (a), Harrieth Wagner (a), Tom D. Brutsaert (a), Max Gassmann (b) and Peter D. Wagner (a)
Respiratory Physiology & Neurobiology Volume 144, Issue 1 , 30 November 2004, Pages 71-80
Abstract
To determine if hypoxia-inducible factor-1 (HIF-1) may regulate skeletal muscle vascular endothelial growth factor (VEGF) expression in response to exercise or hypoxia, rats underwent 1 h sciatic nerve electrical stimulation (ES), hypoxic exposure (H) or combined stimuli. HIF-1 protein levels increased six-fold with maximal (8 V) ES with or without H. Similar HIF-1 increases occurred with sub-maximal (6 V and 4 V) ES plus H, but not in sub-maximal ES or H alone. VEGF mRNA and protein levels increased three-fold in sub-maximal ES or H alone, six-fold in sub-maximal ES plus H, 6.3-fold with maximal ES, and 6.5-fold after maximal ES plus H. These data suggest: (1) intracellular hypoxia during normoxic exercise may exceed that during 8% oxygen breathing at rest and is more effective in stimulating HIF-1; (2) HIF-1 may be an important regulator of exercise-induced VEGF transcription; and (3) breathing 8% O2 does not alter HIF-1 expression in skeletal muscle, implying that exercise-generated signals contribute to the regulation of HIF-1 and/or VEGF.
Author Keywords: Exercise; VEGF; Hypoxia; Skeletal muscle; Mammals; Rat; Modulators; HIF-1; Muscle; Skeletal; VEGF expression
Corresponding author. Tel.: +1 858 534 6967; fax: +1 858 534 4812.
(a) Division of Physiology (0623A), Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA
(b) Institute of Veterinary Physiology, University of Zürich-Irchel, CH-8057, Zurich, Switzerland. | 
