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Angiotensin II causes vascular inflammation via activation of μ‐calpain
Author(s) -
Scalia Rosario,
Gong Yulan,
Berzins Brett
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.a703-d
Subject(s) - calpain , angiotensin ii , intravital microscopy , microcirculation , medicine , endocrinology , vascular permeability , inflammation , extravasation , chemistry , pharmacology , immunology , receptor , biochemistry , enzyme
Hyperglycemia increases tissue angiotensin II (AngII) levels, which induces endothelial dysfunction and vascular inflammation. We have previously reported that hyperglycemia increases μ‐calpain activity causing loss of endothelial nitric oxide and increased leukocyte trafficking in the microcirculation. We report now evidence that links the inflammatory action of AngII to μ‐calpain activity. We studied leukocyte‐endothelial cell interactions in rats injected with a sub‐pressor dose of AngII (23 ng/kg/ip, 18 hrs before study), using intravital microscopy of mesenteric post‐capillary venules. AngII increased leukocyte rolling, adhesion and extravasation in the rat mesentery (p<0.01 vs vehicle), in the absence of relevant hemodynamic changes. AngII also increased albumin permeability in the microcirculation, as detected by Texas Red‐conjugated albumin (p<0.01). These inflammatory effects of AngII were blocked by administration of the selective calpain inhibitor ZLLal (72 μg/Kg/ip, 18 hrs before study). Western blot analyses of the ubiquitously expressed μ‐ and m‐calpain isoforms in vascular segments of the rat mesentery, demonstrated increased μ‐calpain activity in response to AngII. Our data provide a new mechanism for the inflammatory actions of the renin/angiotensin system and further support a role for calpains in diabetic vascular complications. (Supported by NIH Grant # R01DK064344)