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

Abstract：

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 radioimmuno 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.

journal_name

J Hypertens

journal_title

Journal of hypertension

authors

Chun TH,Itoh H,Saito T,Yamahara K,Doi K,Mori Y,Ogawa Y,Yamashita J,Tanaka T,Inoue M,Masatsugu K,Sawada N,Fukunaga Y,Nakao K

doi

10.1097/00004872-200018050-00010

subject

Has Abstract

pub_date

2000-05-01 00:00:00

pages

575-80

issue

eissn

0263-6352

issn

1473-5598

journal_volume

pub_type

杂志文章

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