{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:30:15Z","timestamp":1783488615381,"version":"3.55.0"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2000,8]]},"abstract":"<jats:p><jats:italic>Abstract<\/jats:italic>\u2014The effects of bradykinin on the regulatory mechanisms of prostacyclin synthesis in endothelial cells were investigated in association with intracellular Ca<jats:sup>2+<\/jats:sup>kinetics, cytosolic phospholipase A<jats:sub>2<\/jats:sub>(cPLA<jats:sub>2<\/jats:sub>) activity, and mRNA expression of cPLA<jats:sub>2<\/jats:sub>and prostaglandin H synthase (PGHS) isoforms. Bradykinin enhanced prostacyclin release from endothelial cells time-dependently, but pretreatment with EGTA H-7 or HOE 140 inhibited bradykinin-induced prostacyclin release. Bradykinin increased both the influx of extracellular Ca<jats:sup>2+<\/jats:sup>and Ca<jats:sup>2+<\/jats:sup>release from the intracellular Ca<jats:sup>2+<\/jats:sup>storage sites. These reactions occurred within 5 minutes after bradykinin stimulation. Within 15 minutes, bradykinin activated cPLA<jats:sub>2<\/jats:sub>to 1.3-fold the control level. The constitutive expressions of mRNA of cPLA<jats:sub>2<\/jats:sub>, PGHS-1, and PGHS-2 was 87, 562, and 47 amol\/\u03bcg RNA, respectively. With the stimulation of bradykinin, cPLA<jats:sub>2<\/jats:sub>mRNA increased to 746 amol\/\u03bcg RNA in 15 minutes, PGHS-1 mRNA increased to 10 608 amol\/\u03bcg RNA, and PGHS-2 mRNA increased to 22 400 amol\/\u03bcg RNA in 180 minutes. Pretreatment with cycloheximide superinduced cPLA<jats:sub>2<\/jats:sub>and PGHS-2 mRNA expression but almost completely inhibited PGHS-1. Pretreatment with EGTA had effects similar to pretreatment with cycloheximide in the case of cPLA<jats:sub>2<\/jats:sub>and PGHS-1 but did not affect PGHS-2. These findings suggest that the elevation of cPLA<jats:sub>2<\/jats:sub>activity caused by the increase of intracellular Ca<jats:sup>2+<\/jats:sup>concentration is important in the early phase of bradykinin-induced prostacyclin synthesis and that the mechanisms regulating cPLA<jats:sub>2<\/jats:sub>are different from those regulating PGHS isoforms in endothelial cells.<\/jats:p>","DOI":"10.1161\/01.hyp.36.2.201","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:25:31Z","timestamp":1339460731000},"page":"201-207","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Effects of Bradykinin on Prostaglandin I<sub>2<\/sub>Synthesis in Human Vascular Endothelial Cells"],"prefix":"10.1161","volume":"36","author":[{"given":"Seiki","family":"Yamasaki","sequence":"first","affiliation":[{"name":"From the Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohei","family":"Sawada","sequence":"additional","affiliation":[{"name":"From the Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumio","family":"Komatsu","sequence":"additional","affiliation":[{"name":"From the Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Kawahara","sequence":"additional","affiliation":[{"name":"From the Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Tsuda","sequence":"additional","affiliation":[{"name":"From the Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Sato","sequence":"additional","affiliation":[{"name":"From the Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihisa","family":"Toratani","sequence":"additional","affiliation":[{"name":"From the Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihito","family":"Kono","sequence":"additional","affiliation":[{"name":"From the Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Higaki","sequence":"additional","affiliation":[{"name":"From the Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Imamura","sequence":"additional","affiliation":[{"name":"From the Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Tada","sequence":"additional","affiliation":[{"name":"From the Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoaki","family":"Akamatsu","sequence":"additional","affiliation":[{"name":"From the Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Tamagaki","sequence":"additional","affiliation":[{"name":"From the Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Tsuji","sequence":"additional","affiliation":[{"name":"From the Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"From the Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_1_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-90-1-19"},{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S0022-3565(25)21179-X","volume":"279","year":"1996","unstructured":"Brown NJ, Ryder D, Gainer JV, Morrow JD, Nadeau J. 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