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Matrix metalloproteinase‐inhibition prevents the acute inward remodeling induced by prolonged vasoconstriction in isolated arterioles
Author(s) -
MartinezLemus Luis A.,
Zhao Guiling,
Bosanquet James P.
Publication year - 2008
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.22.2_supplement.56
Subject(s) - vasoconstriction , cremaster muscle , matrix metalloproteinase , arteriole , medicine , endocrinology , extracellular matrix , chemistry , angiotensin ii , circulatory system , microcirculation , receptor , biochemistry
Inward remodeling induced by prolonged vasoconstriction in isolated arterioles is associated with the repositioning of vascular smooth muscle (VSM) cells within the arteriolar wall. We hypothesize that this process requires partial degradation of the extracellular matrix to allow for the repositioning of VSM cells and the reduction of passive diameter (inward remodeling). Experiments were performed in isolated and pressurized (60 mmHg) rat cremaster arterioles. Results indicated that exposure to norepinephrine (NE, 10 −5.5 M) plus angiotensin‐II (Ang‐II, 10 −7 M) for 4 hours induced inward remodeling and increased the in situ and tissue zymography gelatinolytic activity of arterioles (5 fold vs. time controls, P<0.05). Real time PCR results further suggest that MMP‐2 and ‐9 are upregulated by exposure to the agonists. Incubation with the MMP‐inhibitor GM6001 (15 μM) significantly reduced gelatinolytic activity and prevented the development of inward remodeling without inhibiting the vasoconstriction induced by NE and Ang‐II. These results: 1) indicate that MMPs, in particular the gelatinases, may play a role in the development of inward remodeling in the resistance vasculature; 2) highlight the rapid plasticity of the vascular wall; and 3) suggest that persistent vasoconstriction requires MMP activation to induce acute inward remodeling in resistance vessels. Funded by AHA.