{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T15:02:10Z","timestamp":1783350130616,"version":"3.54.6"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":425,"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":[[2007,12]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>The mechanism for the development of post\u2010haemorrhagic cerebral vasospasm after subarachnoid haemorrhage (SAH) still remains unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>We investigated the role of thrombin and its receptor PAR<jats:sub>1<\/jats:sub>in the development of hyper\u2010contractility of the basilar artery in a rabbit double haemorrhage model, which received two injections of autologous blood into the cisterna magna.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>In the basilar artery isolated from the control rabbits, thrombin, only at 10\u2003units\u2003ml<jats:sup>\u22121<\/jats:sup>, induced a transient endothelium\u2010dependent relaxation and a slight smooth muscle contraction. In SAH, the contractile response to thrombin was markedly enhanced, while the endothelium\u2010dependent relaxant effect of thrombin remained unchanged. The enhancement of the contractile responses was also observed in the absence of endothelium and thrombin induced an enhanced contraction at concentrations higher than 0.3\u2003units\u2003ml<jats:sup>\u22121<\/jats:sup>. The contractile response to PAR<jats:sub>1<\/jats:sub>\u2010activating peptide was also enhanced after SAH. However, the contractile responses to high K<jats:sup>+<\/jats:sup>and endothelin\u20101, and the myofilament Ca<jats:sup>2+<\/jats:sup>\u2010sensitivity remained unchanged after SAH. An immunoblot analysis suggested the up\u2010regulation of PAR<jats:sub>1<\/jats:sub>in the smooth muscle of the basilar artery. The heparinization of blood before injection prevented the enhancement of the contractile responses to thrombin and PAR<jats:sub>1<\/jats:sub>\u2010activating peptide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and implications:<\/jats:title><jats:p>The present study demonstrated, for the first time, that the contractile response of the basilar artery to thrombin was markedly enhanced after SAH. Mechanistically, our findings suggested that the activation of thrombin following hemorrhage up\u2010regulated the expression of PAR<jats:sub>1<\/jats:sub>, thereby inducing the hyper\u2010responsiveness to thrombin.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(2007)<jats:bold>152<\/jats:bold>, 1131\u20131139; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0707435\">10.1038\/sj.bjp.0707435<\/jats:ext-link>; published online 3 September 2007<\/jats:p><\/jats:sec>","DOI":"10.1038\/sj.bjp.0707435","type":"journal-article","created":{"date-parts":[[2007,9,3]],"date-time":"2007-09-03T07:50:12Z","timestamp":1188805812000},"page":"1131-1139","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Up\u2010regulation of proteinase\u2010activated receptor 1 and increased contractile responses to thrombin after subarachnoid haemorrhage"],"prefix":"10.1111","volume":"152","author":[{"given":"Y","family":"Maeda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Hirano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Kai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Hirano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S O","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Kanaide","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"6044","DOI":"10.1016\/S0021-9258(18)42659-2","article-title":"Homologous desensitization of HEL cell thrombin receptors. 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