In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 36, No. 2 ( 2000-08), p. 201-207
Abstract:
Abstract —The effects of bradykinin on the regulatory mechanisms of prostacyclin synthesis in endothelial cells were investigated in association with intracellular Ca 2+ kinetics, cytosolic phospholipase A 2 (cPLA 2 ) activity, and mRNA expression of cPLA 2 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 2+ and Ca 2+ release from the intracellular Ca 2+ storage sites. These reactions occurred within 5 minutes after bradykinin stimulation. Within 15 minutes, bradykinin activated cPLA 2 to 1.3-fold the control level. The constitutive expressions of mRNA of cPLA 2 , PGHS-1, and PGHS-2 was 87, 562, and 47 amol/μg RNA, respectively. With the stimulation of bradykinin, cPLA 2 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 cPLA 2 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 2 and PGHS-1 but did not affect PGHS-2. These findings suggest that the elevation of cPLA 2 activity caused by the increase of intracellular Ca 2+ concentration is important in the early phase of bradykinin-induced prostacyclin synthesis and that the mechanisms regulating cPLA 2 are different from those regulating PGHS isoforms in endothelial cells.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/01.HYP.36.2.201
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2000
detail.hit.zdb_id:
2094210-2
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