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.