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Hypoxia and expression of VEGF-A protein in relation to capillary growth in electrically stimulated rat and rabbit skeletal muscles

Published online by Cambridge University Press:  21 May 2002

O. Hudlicka ,
M. Milkiewicz ,
M. A. Cotter  and
M. D. Brown
O. Hudlicka
Affiliation:
Department of Physiology and School of Sport and Exercise Sciences, University of Birmingham, Birmingham B15 2TT and Department of Biomedical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK
M. Milkiewicz
Affiliation:
Department of Physiology and School of Sport and Exercise Sciences, University of Birmingham, Birmingham B15 2TT and Department of Biomedical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK
M. A. Cotter
Affiliation:
Department of Physiology and School of Sport and Exercise Sciences, University of Birmingham, Birmingham B15 2TT and Department of Biomedical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK
M. D. Brown
Affiliation:
Department of Physiology and School of Sport and Exercise Sciences, University of Birmingham, Birmingham B15 2TT and Department of Biomedical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK
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Abstract

To investigate the role of hypoxia as a stimulus to the early upregulation of vascular endothelial growth factor (VEGF) in fast skeletal muscles during chronic low frequency stimulation, blood flow, oxygen consumption, VEGF expression and capillary:fibre ratio were measured in chronically stimulated tibialis anterior and extensor digitorum longus (EDL) muscles in rabbits and rats. No differences were found in blood flow, oxygen consumption and extraction between rabbit muscles stimulated for 2 or 4 days (8 h on-16 h off) and controls. Muscle PO2 polarographically measured immediately at the end of stimulation on day 2 was also no different from control under resting conditions (10.7 ± 1.6 vs. 9.5 ± 1.2 Torr, n.s.). Unlike control muscles, however, PO2 in 2 day stimulated muscles did not increase immediately after a further acute bout of contractions. This difference was not apparent after similar acute contractions in 4 day stimulated muscles. The involvement of VEGF in early angiogenesis in stimulated muscles was studied in serial cryosections of rat EDL. The proportion of capillaries positively immunostained for VEGF increased from 25 ± 1 % to 40 ± 1 % (P < 0.05) in muscles removed on day 2 immediately at the end of chronic stimulation; it decreased slightly after 16 h rest, and increased again after 4 days of stimulation. Capillary:fibre ratio was unchanged throughout the experiment. Capillary cell proliferation increased only after the rest period on day 2 (20-fold increase) and day 4 (12-fold increase), indicating angiogenesis in progress. Thus the timing of transient hypoxia and increase in capillary-linked VEGF in stimulated muscles, albeit in different species, was similar, and increased VEGF staining and capillary cell proliferation occurred even after the hypoxia had resolved. This suggests (1) a connection between hypoxia and VEGF during the early stages of stimulation, although ensuing capillary proliferation may thereafter rapidly correct for local hypoxia, and (2) that the subsequent angiogenesis and VEGF expression are dependent on factors other than hypoxia. Experimental Physiology (2002) 87.3, 373-381.

Type
Full Length Papers
Information
Experimental Physiology , Volume 87 , Issue 3 , May 2002 , pp. 373 - 381
Copyright
© The Physiological Society 2002

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