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First published online on December 13, 2002.
Copyright © 2002 by The Physiological Society
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2002.030569v1
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Received August 9, 2002
Accepted after revision November 21, 2002

The effect of chronic skeletal muscle stimulation on capillary growth in the rat: are sensory nerve fibres involved?

O. Hudlicka1*, Laura Graciotti2, Gianluca Fulgenzi2, Margaret D. Brown3, Malgorzata Milkiewicz4, and Anna-Luisa Granata2

1 Department of Physiology, University of Birmingham Medical School, Birmingham B15 2TT, UK
2 Department of Experimental Pathology, University of Ancona, Ancona, Italy
3 School of Sport and Exercise Sciences, University of Birmingham, Birmingham, UK
4 Department of Physiology and School of Sport and Exercise Sciences, University of Birmingham, Birmingham, UK

* To whom correspondence should be addressed. E-mail: o.hudlicka{at}bham.ac.uk.

Indirect chronic electrical stimulation of skeletal muscle activates not only efferent but also afferent nerve fibres. To investigate effects specific to this on capillary growth, one of the earliest changes, cell proliferation and capillary ultrastructure were studied in ankle flexors of rats with and without deafferentation of the stimulated side. Two weeks after preganglionic section of dorsal roots L4-L6, the peroneal nerve was stimulated (10 Hz, 8 h day-1) for 2 or 7 days. Proliferating nuclei labelled by bromodeoxyuridine or proliferating cell nuclear antigen staining were colocalized to alkaline phosphatase-stained capillaries (Lc) or other interstitial nuclei (Li) in frozen sections of extensor digitorum longus. Capillary fine structure was examined in extensor hallucis proprius by transmission electron microscopy. The stimulation-induced increase in capillary and interstitial proliferation (Lc 9.9 ± 1.9 %, Li 8.8 ± 2.1 % vs. Lc 2.6 ± 0.4 %, Li 1.9 ± 0.3 % in controls, P < 0.05) was depressed at 2 days by dorsal root section (Lc 4.8 ± 0.7 %, Li 3.2 ± 0.9 %, P < 0.05), an effect likely to be mainly on fibroblasts; no depression was seen at 7 days. Dorsal root section reduced stimulation-induced capillary endothelial swelling at both time points. In contralateral muscles of intact rats, stimulation increased interstitial cell proliferation and capillary swelling, both effects being eliminated by dorsal root section. Capillary growth induced by stimulation (24 % increase in capillary : fibre ratio at 7 days) was unaffected by deafferentation. The reduction in capillary ultrastructural changes and interstitial proliferation in both stimulated and contralateral muscles implies that stimulation of afferent fibres leads directly to release of humoral factors and/or activation via dorsal roots of fibres that release humoral substances. Contralateral muscles are an inadequate control for the effects of chronic stimulation in the intact animal.




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