Preeclamptic serum enhances endothelin-converting enzyme expression in cultured endothelial cells.
Increased vascular sensitivity to vasoconstrictors, such as angiotensin II and epinephrine, is observed in preeclampsia (PE). Recently, it was suggested that abnormal endothelial function might contribute to the pathophysiologic changes in PE. We investigated vasoconstrictor (angiotensin II and epinephrine)-induced endothelin-1 (ET-1) release from human umbilical vein endothelial cells incubated with sera from women with PE compared with normotensive pregnant and nonpregnant women. Moreover, inositol 1,4,5-trisphosphate production and endothelin-converting enzyme (ECE) expression in human umbilical vein endothelial cells were also evaluated. There were no significant differences in ET-1 release without vasoconstrictors among the three groups (nonpregnant, normotensive pregnant, and PE). No significant differences in basal inositol 1,4,5-trisphosphate production and ECE expression without vasoconstrictors were detected among the three groups. Vasoconstrictor-induced ET-1 release was significantly increased by PE sera. No significant difference was detected in vasoconstrictor-induced inositol 1,4,5-trisphosphate production among the three groups. However, ECE expression after incubation with vasoconstrictor was significantly increased by PE sera. Our results suggest that ET-1 release from endothelial cells may contribute to the increased vascular sensitivity to vasoconstrictors observed in PE, and that vasoconstrictor-induced ET-1 release may be related to enhanced ECE expression.
Nishikawa
S
S
Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, Japan.
Miyamoto
A
A
Yamamoto
H
H
Ohshika
H
H
Kudo
R
R
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D001790:Blood Physiological Phenomena; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000378:metabolism; D000072396:Endothelin-Converting Enzymes; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D008666:Metalloendopeptidases; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D012016:Reference Values; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D019332:Endothelin-1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D015544:Inositol 1,4,5-Trisphosphate; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; D004837:Epinephrine