{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:23:07Z","timestamp":1790713387545,"version":"4.1.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2001,3,30]]},"abstract":"<jats:p><jats:italic>Abstract<\/jats:italic>\u2014 Flow-dependent dilation is a fundamental mechanism by which large arteries ensure appropriate blood supply to tissues. We investigated whether or not the vascular kallikrein-kinin system, especially tissue kallikrein (TK), contributes to flow-dependent dilation by comparing wild-type and TK-knockout mice in which the presence or absence of TK expression was verified. We examined in vitro changes in the outer diameter of perfused carotid arteries from TK<jats:sup>+\/+<\/jats:sup>and TK<jats:sup>\u2212\/\u2212<\/jats:sup>mice. In both groups, exogenous bradykinin caused a similar dilation that was abolished by the B<jats:sub>2<\/jats:sub>receptor antagonist HOE-140, as well as by the NO synthase inhibitor<jats:italic>N<\/jats:italic><jats:sup>\u03c9<\/jats:sup>-nitro-<jats:sc>l<\/jats:sc>-arginine methyl ester. However, purified kininogen dilated only TK<jats:sup>+\/+<\/jats:sup>arteries, demonstrating the essential role of TK in the vascular formation of kinins. In TK<jats:sup>+\/+<\/jats:sup>arteries, increasing intraluminal flow caused a larger endothelium-dependent dilation than that seen in TK<jats:sup>\u2212\/\u2212<\/jats:sup>. In both strains the flow response was mediated by NO and by endothelium-derived hyperpolarizing factor, whereas in TK<jats:sup>\u2212\/\u2212<\/jats:sup>vasoconstrictor prostanoids participated as well. HOE-140 impaired flow-dependent dilation in TK<jats:sup>+\/+<\/jats:sup>arteries while showing no effect in TK<jats:sup>\u2212\/\u2212<\/jats:sup>. This compound reduced the flow response in TK<jats:sup>+\/+<\/jats:sup>arteries to a level similar to that in TK<jats:sup>\u2212\/\u2212<\/jats:sup>. After NO synthase inhibition, HOE-140 no longer affected the response of TK<jats:sup>+\/+<\/jats:sup>. Impaired flow-dependent dilation was also observed in arteries from knockout mice lacking bradykinin B<jats:sub>2<\/jats:sub>receptors as compared with wild-type animals. This study demonstrates the active contribution of the vascular kallikrein-kinin system to one-third of the flow-dependent dilation response via activation of B<jats:sub>2<\/jats:sub>receptors coupled to endothelial NO release.<\/jats:p>","DOI":"10.1161\/01.res.88.6.593","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:52:16Z","timestamp":1339462336000},"page":"593-599","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":104,"title":["Decreased Flow-Dependent Dilation in Carotid Arteries of Tissue Kallikrein\u2013Knockout Mice"],"prefix":"10.1161","volume":"88","author":[{"given":"Sonia","family":"Bergaya","sequence":"first","affiliation":[{"name":"From the Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Unit 541 (S.B., E.M., B.I.L., C.M.B.), Ho\u0302pital Lariboisie\u0300re, and Unit 367 (P.M., M.B.-F., F.A.-G.), Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Meneton","sequence":"additional","affiliation":[{"name":"From the Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Unit 541 (S.B., E.M., B.I.L., C.M.B.), Ho\u0302pital Lariboisie\u0300re, and Unit 367 (P.M., M.B.-F., F.A.-G.), Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May","family":"Bloch-Faure","sequence":"additional","affiliation":[{"name":"From the Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Unit 541 (S.B., E.M., B.I.L., C.M.B.), Ho\u0302pital Lariboisie\u0300re, and Unit 367 (P.M., M.B.-F., F.A.-G.), Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Mathieu","sequence":"additional","affiliation":[{"name":"From the Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Unit 541 (S.B., E.M., B.I.L., C.M.B.), Ho\u0302pital Lariboisie\u0300re, and Unit 367 (P.M., M.B.-F., F.A.-G.), Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franc\u0327ois","family":"Alhenc-Gelas","sequence":"additional","affiliation":[{"name":"From the Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Unit 541 (S.B., E.M., B.I.L., C.M.B.), Ho\u0302pital Lariboisie\u0300re, and Unit 367 (P.M., M.B.-F., F.A.-G.), Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard I.","family":"Le\u0301vy","sequence":"additional","affiliation":[{"name":"From the Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Unit 541 (S.B., E.M., B.I.L., C.M.B.), Ho\u0302pital Lariboisie\u0300re, and Unit 367 (P.M., M.B.-F., F.A.-G.), Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal M.","family":"Boulanger","sequence":"additional","affiliation":[{"name":"From the Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale, Unit 541 (S.B., E.M., B.I.L., C.M.B.), Ho\u0302pital Lariboisie\u0300re, and Unit 367 (P.M., M.B.-F., F.A.-G.), Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.8.1.37"},{"key":"e_1_3_2_2_2","first-page":"H1145","volume":"250","year":"1986","unstructured":"Rubanyi GM, Romero JC, Vanhoutte PM. 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