Egginton, S orcid.org/0000-0002-3084-9692, Hussain, A, Hall-Jones, J et al. (3 more authors) (2016) Shear stress-induced angiogenesis in mouse muscle is independent of the vasodilator mechanism and quickly reversible. Acta Physiologica, 218 (3). pp. 153-166. ISSN 1748-1708
Abstract
Aim: Is modulation of skeletal muscle capillary supply by altering blood flow due to a presumptive shear stress response per se, or dependent on the vasodilator mechanism? Methods: The response to four different vasodilators, and cotreatment with blockers of NO and prostaglandin synthesis, was compared. Femoral artery blood flow was correlated with capillary-to-fibre ratio (C:F) and protein levels of putative angiogenic compounds. Results: All vasodilators induced a similar increase in blood flow after 14 days, with a similar effect on C:F (1.62 ± 0.05, 1.60 ± 0.01, 1.57 ± 0.06, 1.57 ± 0.07, respectively, all P < 0.05 vs. control 1.20 ± 0.01). Concomitant inhibitors revealed differential effects on blood flow and angiogenesis, demonstrating that a similar response may have different signalling origins. The time course of this response with the most commonly used vasodilator, prazosin, showed that blood flow increased from 0.40 mL min−1 to 0.61 mL min−1 by 28 days (P < 0.05), dropped within 1 week after the cessation of treatment (0.54 mL min−1; P < 0.05) and returned to control levels by 6 weeks. In parallel with FBF, capillary rarefaction began within 1 week (P < 0.05), giving C:F values similar to control by 2 weeks. Of the dominant signalling pathways, prazosin decreased muscle VEGF, but increased its cognate receptor Flk-1 (both P < 0.01); levels of eNOS varied with blood flow (P < 0.05), and Ang-1 initially increased, while its receptor Tie-2 was unchanged, with only modest changes in the antiangiogenic factor TSP-1. Conclusion: Hyperaemia-induced angiogenesis, likely in response to elevated shear stress, is independent of the vasodilator involved, with a rapid induction and quick regression following the stimulus withdrawal.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd. This is the peer reviewed version of the following article: Egginton, S., Hussain, A., Hall-Jones, J., Chaudhry, B., Syeda, F. and Glen, K. E. (2016), Shear stress-induced angiogenesis in mouse muscle is independent of the vasodilator mechanism and quickly reversible. Acta Physiologica. doi: 10.1111/apha.12728, which has been published in final form at http://dx.doi.org/10.1111/apha.12728. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. |
Keywords: | cromakalim; EDL ; ethanol; prazosin; VEGF; verapamil |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 18 Jul 2016 09:03 |
Last Modified: | 18 Jul 2017 06:26 |
Published Version: | http://dx.doi.org/10.1111/apha.12728 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1111/apha.12728 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:102464 |