Shear stress augments expression of C-type natriuretic peptide and adrenomedullin

Tae Hwa Chun, Hiroshi Itoh, Yoshihiro Ogawa, Naohisa Tamura, Kazuhiko Takaya, Toshio Igaki, Jun Yamashita, Kentaro Doi, Mayumi Inoue, Ken Masatsugu, Risa Korenaga, Joji Ando, Kazuwa Nakao

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

Shear stress is known to dilate blood vessels and exert antiproliferative effects on vascular walls; these effects have been ascribed to shear stress-induced upregulation of endothelium-derived vasoactive substances, mainly nitric oxide and prostacyclin. We have demonstrated the significance of C-type natriuretic peptide (CNP) as a novel endothelium- derived relaxing peptide (EDRP) that shares a cGMP pathway with nitric oxide. Adrenomedullin is a recently isolated EDRP that elevates intracellular cAMP as prostacyclin does. To elucidate the possible role of these EDRPs under shear stress, we examined the effect of physiological shear stress on CNP mRNA expression in endothelial cells derived from the human umbilical vein (HUVECs), bovine aorta (BAECs), and murine lymph nodes (MLECs) as well as adrenomedullin mRNA expression in HUVECs. CNP mRNA was stimulated prominently in HUVECs under shear stress of 15 dyne/cm2 in a time-dependent manner (4 hours, sixfold increase compared with that in the static condition; 24 hours, 30-fold increase). Similar results were obtained in BAECs (4 hours, twofold increase; 24 hours, threefold increase) and MLECs (4 hours, threefold increase; 24 hours, 10-fold increase). Augmentation of CNP mRNA expression that was dependent on shear stress intensity was also observed (5 dyne/cm2, 2.5-fold increase of static; 15 dyne/cm2, 4.5-fold increase). Increased CNP secretion was also confirmed by the specific radio-immunoassay for CNP, Adrenomedullin mRNA expression in HUVECs increased under shear stress of 15 dyne/cm2 in a time-dependent manner (4 hours, 1.2-fold increase of static; 24 hours, threefold increase) and shear stress intensity-dependent manner (15 dyne/cm2, threefold increase compared with that at 5 dyne/cm2). These results suggest that the coordinated augmentation of mRNA expression of these novel EDRPs may constitute shear stress-dependent vasodilator and antiproliferative effects.

Original languageEnglish
Pages (from-to)1296-1302
Number of pages7
JournalHypertension
Volume29
Issue number6
DOIs
Publication statusPublished - 1997 Jun
Externally publishedYes

Keywords

  • adrenomedullin
  • atrial natriuretic factor
  • endothelium
  • nitric oxide
  • prostacyclin

ASJC Scopus subject areas

  • Internal Medicine

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