Combined effect of bradykinin B2 and neurokinin-1 receptor activation on endothelial cell proliferation in acute synovitis.
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 NK1 or B2 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 NK1 and B2 receptors inhibited 64% of the synovitis-enhanced endothelial cell proliferation. Synovitis-enhanced endothelial cell proliferation was also inhibited by the B2 receptor antagonist alone (27%) but not by the NK1 receptor antagonist alone. B1 receptor agonist (des-Arg9-bradykinin) and antagonist (SR240612A) did not significantly modulate endothelial cell proliferation. B2 receptor mRNA was constitutively expressed in both mild and moderate inflammation, whereas B1 mRNA production was induced in the moderate inflammation model. These findings demonstrate that substance P and bradykinin can act on NK1 and B2 receptors, respectively, to promote endothelial cell proliferation in acute synovitis.
Seegers
Hélène C
HC
Academic Rheumatology, University of Nottingham, City Hospital, Nottingham, UK. helene.seegers@univ-angers.fr
Avery
Paul S
PS
McWilliams
Daniel F
DF
Haywood
Lyane
L
Walsh
David A
DA
D000208:Acute Disease; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists; D002455:Cell Division; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D008954:Models, Biological; D064729:Neurokinin-1 Receptor Antagonists; D051381:Rats; D043783:Receptor, Bradykinin B1 / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D013373:Substance P / Q000494:pharmacology; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013585:Synovitis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
D065094:Bradykinin B2 Receptor Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018040:Receptors, Neurokinin-1; D013373:Substance P; D001920:Bradykinin