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

被引:74
作者
Chun, TH [1 ]
Itoh, H [1 ]
Saito, T [1 ]
Yamahara, K [1 ]
Doi, K [1 ]
Mori, Y [1 ]
Ogawa, Y [1 ]
Yamashita, J [1 ]
Tanaka, T [1 ]
Inoue, M [1 ]
Masatsugu, K [1 ]
Sawada, N [1 ]
Fukunaga, Y [1 ]
Nakao, K [1 ]
机构
[1] Kyoto Univ, Grad Sch Med, Dept Med & Clin Sci, Sakyo Ku, Kyoto 6068507, Japan
关键词
natriuretic peptide; adrenomedullin; oxidative stress; endothelial cells; hydrogen peroxide; N-acetylcysteine;
D O I
10.1097/00004872-200018050-00010
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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/ I) 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 radioimmun assays 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. I Hypertens 2000, 18:575-580 (C) Lippincott Williams & Wilkins.
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页码:575 / 580
页数:6
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