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(Hypertension. 2000;36:201.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Effects of Bradykinin on Prostaglandin I₂ Synthesis in Human Vascular Endothelial Cells

Seiki Yamasaki; Shohei Sawada; Sumio Komatsu; Takeshi Kawahara; Yutaka Tsuda; Toshiyuki Sato; Akihisa Toratani; Yoshihito Kono; Tadashi Higaki; Hitoshi Imamura; Yusuke Tada; Naoaki Akamatsu; Toshiyuki Tamagaki; Hajime Tsuji; Masao Nakagawa

From the Second Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Correspondence to Sumio Komatsu, MD, Second Department of Medicine, Kyoto Prefectural University of Medicine, 465, Kajii-cho, Kawaramachi-Hirokoji agaru, Kamigyo-ku, Kyoto 602-8566, Japan. E-mail sawada{at}koto.kpu-m.ac.jp

Abstract—The effects of bradykinin on the regulatory mechanisms of prostacyclin synthesis in endothelial cells were investigated in association with intracellular Ca²⁺ kinetics, cytosolic phospholipase A₂ (cPLA₂) activity, and mRNA expression of cPLA₂ 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 Ca²⁺ and Ca²⁺ release from the intracellular Ca²⁺ storage sites. These reactions occurred within 5 minutes after bradykinin stimulation. Within 15 minutes, bradykinin activated cPLA₂ to 1.3-fold the control level. The constitutive expressions of mRNA of cPLA₂, PGHS-1, and PGHS-2 was 87, 562, and 47 amol/µg RNA, respectively. With the stimulation of bradykinin, cPLA₂ mRNA increased to 746 amol/µg RNA in 15 minutes, PGHS-1 mRNA increased to 10 608 amol/µg RNA, and PGHS-2 mRNA increased to 22 400 amol/µg RNA in 180 minutes. Pretreatment with cycloheximide superinduced cPLA₂ 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 cPLA₂ and PGHS-1 but did not affect PGHS-2. These findings suggest that the elevation of cPLA₂ activity caused by the increase of intracellular Ca²⁺ concentration is important in the early phase of bradykinin-induced prostacyclin synthesis and that the mechanisms regulating cPLA₂ are different from those regulating PGHS isoforms in endothelial cells.

Key Words: bradykinin • prostacyclin • kinetics, calcium • phospholipases A • prostaglandin H synthase • polymerase chain reaction

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