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Combined effect of bradykinin B 2 and neurokinin‐1 receptor activation on endothelial cell proliferation in acute synovitis.
Author(s) -
Seegers Hélène C.,
Avery Paul S.,
McWilliams Daniel F.,
Haywood Lyane,
Walsh David A.
Publication year - 2004
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/fj.03-0727fje
Subject(s) - bradykinin , synovitis , receptor , medicine , angiogenesis , endocrinology , endothelial stem cell , inflammation , receptor antagonist , agonist , chemistry , cancer research , arthritis , antagonist , biochemistry , in vitro
During acute synovitis, early angiogenesis may enhance inflammation by facilitating edema formation and cellular infiltration. We have investigated the in vivo modulation by bradykinin of neurally enhanced early angiogenesis in rat models of knee synovitis. The increased endothelial cell proliferation that was observed 24 h after intra‐articular injection of substance P (10 nmols) was completely blocked by either NK 1 or B 2 receptor antagonists (SR140333 or FR172357, respectively). In mild synovitis induced by 0.03% Carrageenan, but not in naïve animals, injection of bradykinin (100 nmols) increased endothelial cell proliferation. In moderate synovitis induced by 3% kaolin and 3% carrageenan, the combined blockade of both NK 1 and B 2 receptors inhibited 64% of the synovitis‐enhanced endothelial cell proliferation. Synovitis‐enhanced endothelial cell proliferation was also inhibited by the B 2 receptor antagonist alone (27%) but not by the NK 1 receptor antagonist alone. B 1 receptor agonist (des‐Arg 9 ‐bradykinin) and antagonist (SR240612A) did not significantly modulate endothelial cell proliferation. B 2 receptor mRNA was constitutively expressed in both mild and moderate inflammation, whereas B 1 mRNA production was induced in the moderate inflammation model. These findings demonstrate that substance P and bradykinin can act on NK 1 and B 2 receptors, respectively, to promote endothelial cell proliferation in acute synovitis.