{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:50:49Z","timestamp":1791121849130,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,5,17]],"date-time":"2012-05-17T00:00:00Z","timestamp":1337212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold>We have tested the hypothesis that calcitonin gene\u2010related peptide (CGRP) is a mediator of capsaicin\u2010induced angiogenesis<jats:italic>in vivo<\/jats:italic>.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold>In a series of experiments, the knee joints of rats were injected with CGRP, capsaicin or vehicle control. Groups of animals (<jats:italic>n<\/jats:italic>\u2003=\u20036) were treated with the CGRP receptor antagonist BIBN4096BS and\/or the NK<jats:sub>1<\/jats:sub>receptor antagonist SR140333. Endothelium, proliferating endothelial cell nuclei and macrophages were identified 24\u2003h later in the synovium by immunohistochemistry and quantified by image analysis. mRNA for the receptors for CGRP and adrenomedullin were sought in normal and inflamed rat and human synovia using RT\u2010PCR.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold>Intra\u2010articular CGRP injection increased the endothelial cell proliferation index, whereas macrophage infiltration and knee joint diameters were similar to saline\u2010injected controls<jats:bold>.<\/jats:bold>CGRP\u2010induced endothelial cell proliferation was dose\u2010dependently inhibited by BIBN4096BS. mRNA for adrenomedullin and the CGRP receptor subunits were detected in normal and inflamed human and rat synovia. In capsaicin\u2010induced synovitis, the increased endothelial cell proliferation index was partially blocked by administration of NK<jats:sub>1<\/jats:sub>or CGRP antagonists individually and was reduced to the level of saline controls by coadministration of both receptor antagonists.<\/jats:p><jats:p><jats:bold>CONCLUSIONS AND IMPLICATIONS<\/jats:bold>These data support the hypothesis that CGRP stimulates angiogenesis<jats:italic>in vivo<\/jats:italic>directly by activating CGRP receptors. Capsaicin\u2010induced endothelial cell proliferation was completely blocked by coadministration of CGRP and NK<jats:sub>1<\/jats:sub>receptor antagonists, indicating that both CGRP and substance P may contribute to angiogenesis in this model of synovitis.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2012.01848.x","type":"journal-article","created":{"date-parts":[[2012,1,10]],"date-time":"2012-01-10T13:37:40Z","timestamp":1326202660000},"page":"1261-1271","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["A role for the sensory neuropeptide calcitonin gene\u2010related peptide in endothelial cell proliferation<i>in vivo<\/i>"],"prefix":"10.1111","volume":"166","author":[{"given":"Paul I","family":"Mapp","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel 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