Chronic vasodilation induces matrix metalloproteinase 9 (MMP-9) expression during microvascular remodeling in rat skeletal muscle.
OBJECTIVE
The process of microvessel growth and remodeling depends on the presence of matrix metalloproteinases (MMPs) in a specific spatial pattern of expression. This study characterizes the spatial distribution of metalloproteinase-9 (MMP-9) expression during microvascular remodeling in the rat spinotrapezius muscle.


METHODS
Female Sprague-Dawley rats (4 weeks old) were administered the alpha1-adrenergic blocker prazosin for 7 days to induce chronic vasodilation and associated increases in capillary and arteriolar density. MMP-9 expression was analyzed by Western blotting analysis of microdissected regions of muscle and immunolabeling of muscle sections.


RESULTS
Capillary density expressed as both capillary-to-fiber ratio (C/F) and capillaries per mm2 increased significantly (p < 0.01) due to prazosin administration. Western blotting on microdissected regions of spinotrapezius muscle showed that there was an increase in MMP-9 expression in prazosin-treated animals. Additionally, the Western blots showed a presence of the activated form of MMP-9 in regions of spinotrapezius muscle containing vessels on the order of capillaries and small arterioles. Immunohistochemistry demonstrated that MMP-9 significantly increased in the muscles of treated animals in areas within the vessel walls of microvessels greater than 20 microm in diameter. However, interstitial MMP-9 expression did not significantly increase with prazosin administration.


CONCLUSIONS
These results demonstrate that the expression of MMP-9 increases during in vivo microvascular remodeling in adult skeletal muscle. The MMP-9 expression is limited to larger (>20-microm diameter) microvessels, suggesting a role for MMP-9 in the remodeling of such vessels during prazosin-induced vasodilation and the subsequent capillary proliferation.
Van Gieson
E J
EJ
Department of Biomedical Engineering, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Skalak
T C
TC
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002196:Capillaries / Q000187:drug effects / Q000254:growth & development; D005260:Female; D007150:Immunohistochemistry; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008833:Microcirculation / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000201:enzymology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D020780:Matrix Metalloproteinase 9; D011224:Prazosin