| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
MOLECULAR AND GENOMIC |
1 Angiogenesis Research Group, Centre for Cardiovascular Sciences, University of Birmingham, Birmingham B15 2TT, UK
NO plays a role in a variety of in vitro models of angiogenesis, although confounding effects of NO on non-endothelial tissues make its role during in vivo angiogenesis unclear. We therefore examined the effects of NO on two physiological models of angiogenesis in mouse skeletal muscle: (1) administration of prazosin (50 mg l–1) thereby increasing blood flow; and (2) muscle overload from surgical ablation of a functional synergist. These models induce angiogenesis via longitudinal splitting and capillary sprouting, respectively. Administration of NG-nitro-L-arginine (L-NNA) abolished the increase in capillary to fibre ratio (C:F) in response to prazosin administration, along with the increases in luminal filopodia and large endothelial vacuoles. L-NNA prevented luminal filopodia and vacuolisation in response to extirpation, but had no effect on abluminal sprouting, and little effect on C:F. Comparison of mice lacking endothelial (eNOS–/–) and neuronal NO synthase (nNOS–/–) showed that longitudinal splitting is eNOS-dependent, and Western blotting demonstrated an increase in eNOS but not inducible NOS (iNOS) expression. These data show that there are two pathways of physiological angiogenesis in skeletal muscle characterised by longitudinal splitting and capillary sprouting, respectively. NO generated by eNOS plays an essential role in splitting but not in sprouting angiogenesis, which has important implications for angiogenic therapies that target NO.
(Received 29 July 2005;
accepted after revision 10 November 2005;
first published online 17 November 2005)
Corresponding author S. Egginton: Department of Physiology, The Medical School, The University of Birmingham, Birmingham B15 2TT, UK. Email: s.egginton{at}bham.ac.uk
This article has been cited by other articles:
|
|
 |
|
  A. V. Benest, O. A. Stone, W. H. Miller, C. P. Glover, J. B. Uney, A. H. Baker, S. J. Harper, and D. O. Bates Arteriolar Genesis and Angiogenesis Induced by Endothelial Nitric Oxide Synthase Overexpression Results in a Mature Vasculature Arterioscler. Thromb. Vasc. Biol., August 1, 2008; 28(8): 1462 - 1468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Hellsten, N. Rufener, J. J. Nielsen, B. Hoier, P. Krustrup, and J. Bangsbo Passive leg movement enhances interstitial VEGF protein, endothelial cell proliferation, and eNOS mRNA content in human skeletal muscle Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R975 - R982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Erzurum, S. Ghosh, A. J. Janocha, W. Xu, S. Bauer, N. S. Bryan, J. Tejero, C. Hemann, R. Hille, D. J. Stuehr, et al. Higher blood flow and circulating NO products offset high-altitude hypoxia among Tibetans PNAS, November 6, 2007; 104(45): 17593 - 17598. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Milkiewicz, J. L. Doyle, T. Fudalewski, E. Ispanovic, M. Aghasi, and T. L. Haas HIF-1{alpha} and HIF-2{alpha} play a central role in stretch-induced but not shear-stress-induced angiogenesis in rat skeletal muscle J. Physiol., September 1, 2007; 583(2): 753 - 766. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
