Chronic vasodilation induces matrix metalloproteinase 9 (MMP-9) expressionduring microvascular remodeling in rat skeletal muscle

Objective: The process of microvessel growth and remodeling depends on the presence or matrix metalloproteinases (MMPs) in a specific spatial pattern of expression. This study characterizes the spatial distribution of metallo proteinase-9 (MMP-9) expression during microvascular remodeling in the rat spinotrapezius muscle. Methods: Female Sprague-Dawley rats (4 weeks old) mice administered the alp ha (1)-adrenergic blocker prazosin for 7 days to induce chronic vasodilatio n and associated increases in capillary and arteriolar density. MMP-9 expre ssion was analyzed by Western blotting analysis of microdissected regions o f muscle and immunolabeling of muscle sections. Results: Capillary density expressed as both capillary-to-fiber ratio (C/F) and capillaries per mm(2) increased significantly (p < 0.01) due to prazos in administered . Western blotting on microdissected regions of spinotrapez ius muscle showed that there was an increase in MMP-9 expression in prazosi n-treated animals. Additionally, the Western blots showed a presence of the activated form of MMP-9 in regions of spinotrapezius muscle containing ves sels 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 <m u>m in diameter. However, interstitial MMP-9 expression did not significant ly increase with prazosin administration. Conclusions: These results demonstrate that the expression of MMP-9 increas es during in vivo microvascular remodeling in adult skeletal muscle. The MM P-9 expression is limited to larger (>20-mum diameter) microvessels, sugges ting a role for MMP-9 in the remodeling of such vessels during prazosin-ind uced vasodilation and the subsequent capillary proliferation.