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Matrix metalloproteinase (MMP) inhibition eliminates training‐induced collateral blood flow expansion in rats
Author(s) -
Prior Barry M,
Chen Jianping,
Yang H.T.,
Terjung Ronald L
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a710-d
Subject(s) - sed , blood flow , hindlimb , chemistry , medicine , matrix metalloproteinase , treadmill , collateral circulation , femoral artery , endocrinology , artery , anatomy , zoology , biology
To study the role of MMPs in collateral vessel remodeling, adult male Sprague‐Dawley rats with bilateral femoral artery occlusion (n=30) were divided into sedentary (Sed, limited to cage activity, n=10) or treadmill exercise (Tr, 2x/d, 2 wks; n=20). Rats in Sed or Tr group were fed with either water or MMP inhibitor doxycycline (Doxy; ~30 mg/kg/d) for two wks. Hind limb blood flow was determined with isotope labeled microspheres during treadmill running. In Tr animals, Doxy treatment reduced MMP‐2 protein content by 19% (Western blot); and proMMP‐2 activity by 17% (Zymograph) in the red gastrocnemius muscle when compared with the water controls. Blood pressure (~130 mmHg) and heart rate (~480 bpm) were no difference across the groups during flow measuring. Collateral dependent blood flows to the calf muscle were 48±1.7, 47±8.7, 81±4.1 and 60±3.5 ml/min/100g in Sed+water (n=6), Sed+Doxy (n=4), Tr+water (n=9), and Tr+Doxy (n=8) groups respectively (ANOVA, p<0.001). Maximal luminal diameters of collateral artery (the perforating a.) increased from ~280μm in Sed groups to 317±13.7μm (Tr +water), and reduced to 278±11.3μm by Doxy in the Tr animals. Our results indicate that exercise training‐induced remodeling of collateral function and structure requires normal MMP‐2 function. Supported by NIH HL‐37387.