{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:12:54Z","timestamp":1791216774241,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,5,24]],"date-time":"2004-05-24T00:00:00Z","timestamp":1085356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2004,6]]},"abstract":"<jats:p>The impact of chronic joint inflammation on articular vascular function in rats was investigated to address whether joint swelling and the associated vascular dysfunction are dependent upon a common prostanoid mechanism. Urinary nitrate\/nitrite (NO<jats:sub>x<\/jats:sub>) and PGE<jats:sub>2<\/jats:sub> excretion, knee joint diameter and body weight were measured following induction of adjuvant\u2010induced arthritis (AIA). Ten days postinduction of AIA, joint vascular reactivity was assessed by measuring the perfusion response using a laser Doppler imager (LDI) to topical application of acetylcholine (ACh) and sodium nitroprusside (SNP). Four groups were compared: a non\u2010inflamed control group and three AIA groups treated <jats:sc>i.p.<\/jats:sc> with vehicle, indomethacin or SC\u2010236 (at equimolar doses). The selective cyclooxygenase\u20102 (COX\u20102) inhibitor (SC\u2010236) was used to differentiate between COX\u20101 and \u20102\u2010derived prostaglandins. Urinary NO<jats:sub>x<\/jats:sub> and PGE<jats:sub>2<\/jats:sub> levels increased substantially during the early phase of AIA but decreased thereafter. Toxicity to indomethacin but not SC\u2010236 was observed, as indicated by a marked decrease in body weight. Joint swelling was similarly attenuated by indomethacin and SC\u2010236 (<jats:italic>P<\/jats:italic>= 0.0001 cf. vehicle\u2010treated AIA; <jats:italic>n<\/jats:italic>= 5\u20136 per group), indicating that this is due to COX\u20102 and not COX\u20101 inhibition. The AIA\u2010induced changes in urinary NO<jats:sub>x<\/jats:sub> and PGE<jats:sub>2<\/jats:sub> were corrected by both COX inhibitors. While vascular reactivity to ACh and SNP was significantly attenuated by AIA (<jats:italic>P<\/jats:italic> &lt; 0.002; <jats:italic>n<\/jats:italic>= 5\u201310 per group), the perfusion responses to these vasodilating agents were similar in all three AIA groups, demonstrating that the vascular dysfunction was not corrected by inhibition of either COX\u20101 or COX\u20102 enzymes. Furthermore, the attenuation of both ACh and SNP\u2010induced responses in AIA suggest that vascular dysfunction was not exclusively endothelial in nature. In conclusion, the joint swelling and vascular dysfunction associated with AIA appear to be mediated, at least in part, by independent mechanisms. While COX\u20101\/COX\u20102 inhibition reduced joint swelling, vascular dysfunction in AIA is independent of constitutive or inducible prostanoid mechanisms, and appears not to be solely endothelial\u2010derived, but to involve other components such as the vascular smooth muscle.<\/jats:p>","DOI":"10.1113\/jphysiol.2004.062984","type":"journal-article","created":{"date-parts":[[2004,4,6]],"date-time":"2004-04-06T00:44:11Z","timestamp":1081212251000},"page":"635-643","source":"Crossref","is-referenced-by-count":22,"title":["Pathophysiology of vascular dysfunction in a rat model of chronic joint inflammation"],"prefix":"10.1113","volume":"557","author":[{"given":"Colin G.","family":"Egan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Lockhart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Ferrell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,5,24]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118717"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(93)90071-R"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00204603"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7279"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.013473"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1113\/eph8602129"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(70)80078-X"},{"key":"e_1_2_5_9_1","first-page":"35","article-title":"Essential role for proteinase\u2010activated receptor\u20102 in arthritis","volume":"111","author":"Ferrell WR","year":"2003","journal-title":"et al"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.26.15810"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780390416"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01990957"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(97)00459-0"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/35.8.711"},{"key":"e_1_2_5_15_1","doi-asserted-by":"crossref","first-page":"27357","DOI":"10.1016\/S0021-9258(18)46993-1","article-title":"Investigations of the roles of cysteines in catalysis by prostaglandin endoperoxide synthase","volume":"269","author":"Kennedy TA","year":"1994","journal-title":"J Biol Chem"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(89)91491-8"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00197310"},{"key":"e_1_2_5_18_1","first-page":"776","article-title":"A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2\u2010specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis. 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