Physiological concentration of atrial natriuretic peptide induces endothelial regeneration in vitro

Hyun Kook, Hiroshi Itoh, Bong Seok Choi, Naoki Sawada, Kentaro Doi, Tae Ju Hwang, Kyung Keun Kim, Hiroshi Arai, Yung Hong Baik, Kazuwa Nakao

Research output: Contribution to journalArticlepeer-review

82 Citations (Scopus)


Both nitric oxide (NO) and natriuretic peptides produce apoptosis of vascular smooth muscle cells. However, there is evidence that NO induces endothelial cell proliferation, which suggests that there is a difference in the response of endothelial cells to natriuretic peptides. The purpose of this study was to investigate the effect of atrial natriuretic peptide (ANP) on human endothelial cell survival. ANP within the physiological concentration (10-11 mol/l) induced a 52% increase in the number of human coronary arterial endothelial cells and a 63% increase in human umbilical vein endothelial cells at a low concentration of serum. The increase in cell numbers was blocked by pretreatment with RP8-CPT-cGMP (RP8), a cGMP-dependent protein kinase inhibitor, with wortmannin, an Akt/PKB inhibitor, and with PD-98059, an ERK1/2 inhibitor. In a Transwell migration test, ANP also increased the cell migration, and RP8, wortmannin, and PD-98059 blocked this increase. A wound healing assay was performed to examine the effects of ANP on regeneration in vitro. ANP increased both cell numbers and migration, but the effects were blocked by the above three kinase inhibitors. ANP increased the expression of phospho-Akt and of phospho-ERK1/2 within 1.5 h. These results suggest that ANP can potentiate endothelial regeneration by cGMP-dependent protein kinase stimulation and subsequent Akt and ERK1/2 activations.

Original languageEnglish
Pages (from-to)H1388-H1397
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number4 53-4
Publication statusPublished - 2003 Apr 1
Externally publishedYes


  • Akt/protein kinase B
  • Extracellular signal-regulated kinase 1/2
  • cGMP-dependent protein kinase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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