Possible involvement of oxidative stress in hypoxia-induced adrenomedullin secretion in cultured rat cardiomyocytes.
Although hypoxia induces adrenomedullin gene expression in cultured rat cardiac myocytes, it is still unknown whether oxidative stress is involved in the hypoxia-induced adrenomedullin production. We investigated whether oxidative stress might participate in hypoxia-induced adrenomedullin secretion and whether adrenomedullin might have a protective effect on damaged myocytes. Hypoxia increased adrenomedullin secretion and its gene expression in cardiac myocytes, but not in nonmyocytes. Furthermore, oxidative stress (hydrogen peroxide) also increased adrenomedullin secretion from myocytes. N-acetyl-L-cysteine, a free radical scavenger, completely inhibited the stimulation of adrenomedullin secretion by hydrogen peroxide, and this agent reduced the stimulation of adrenomedullin secretion by hypoxia. Lactate dehydrogenase leakage, a marker of cell injury, was significantly increased with the exposure to hydrogen peroxide and adrenomedullin significantly reduced this leakage. These findings suggest that an oxidative stress may be involved, in part, in the increased adrenomedullin secretion from cardiac myocytes under hypoxic condition. Adrenomedullin secreted from myocytes may play a cell protective role in an autocrine manner.
Yoshihara
Fumiki
F
Research Institute, National Cardiovascular Center, 5-7-1 Fujishirodai, Osaka 565-8565, Suita, Japan. fyoshi@ri.ncvc.go.jp
Horio
Takeshi
T
Nishikimi
Toshio
T
Matsuo
Hisayuki
H
Kangawa
Kenji
K
D000111:Acetylcysteine / Q000494:pharmacology; D053607:Adrenomedullin; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D016166:Free Radical Scavengers / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013997:Time Factors
D000975:Antioxidants; D016166:Free Radical Scavengers; D016877:Oxidants; D010455:Peptides; D012333:RNA, Messenger; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D000111:Acetylcysteine