The rat meniscal transection model of OA reproducibly displays both osteochondral and synovial angiogenesis comparable to our previous observations in human knee OA. DH guinea pigs, by contrast, display low vascularity throughout their protracted course of OA development. Changes in vascularisation occur early during the development of OA in the rat, and may contribute to the pathogenesis of OA.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.