Oxidative stress augments secretion of endothelium-derived relaxing peptides, C-type natriuretic peptide and adrenomedullin

Tae Hwa Chun, Hiroshi Itoh, Takatoshi Saito, Ken Ichi Yamahara, Kentaro Doi, Yuko Mori, Yoshihiro Ogawa, Jun Yamashita, Tokuji Tanaka, Mayumi Inoue, Ken Masatsugu, Naoki Sawada, Yasutomo Fukunaga, Kazuwa Nakao

研究成果: Article査読

80 被引用数 (Scopus)


Objective. Excess oxidative stress is one of the major metabolic abnormalities on vascular walls in hypertension and atherosclerosis. In order to further elucidate the endothelial function under oxidative stress, the effect of hydrogen peroxide (H2O2) on expression of two novel endothelium-derived vasorelaxing peptides, C-type natriuretic peptide (CNP) and adrenomedullin (AM) from bovine carotid artery endothelial cells (BCAECs) was examined. Methods. BCAECs were treated with H2O2 (0.1-1.0 mmol/l) and/or an antioxidant, N-acetylcysteine (NAC) (5-10 mmol/l), and incubated for 48 h. The concentrations of CNP and AM were measured with the specific radioimmunassays that we originally developed. CNP and AM mRNA expressions were also examined by reverse transcription-polymerase chain reaction (RT-PCR). Results. Treatment of BCAECs with 0.5 and 1 mmol/l H2O2 induced 9- and 10-fold increases of CNP concentration in the media. Addition of 10 mmol/l NAC significantly suppressed the effect of H2O2 by 52%. RT-PCR analysis showed that CNP mRNA expression in BCAECs was also rapidly augmented within 1 h with H2O2 (1 mmol/l) treatment, and reached a peak at 3 h to show a 10-fold increase. AM secretion from BCAECs also increased to two-fold with exposure to 0.5 mmol/l H2O2, accompanied with the augmented level of AM mRNA. NAC 10 mmol/l completely suppressed the effect of H2O2 on AM secretion. Conclusions. In this study, it has been demonstrated that H2O2 augments endothelial secretion of the two endothelium-derived relaxing peptides, CNP and AM. Our findings suggest the increased secretion of CNP and AM from endothelium under oxidative stress may function to compensate the impaired nitric oxide-dependent vasorelaxation in hypertension and atherosclerosis. (C) Lippincott Williams and Wilkins.

ジャーナルJournal of hypertension
出版ステータスPublished - 2000 1月 1

ASJC Scopus subject areas

  • 内科学
  • 生理学
  • 循環器および心血管医学


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