Functional reconstitution of endothelial nitric oxide synthase reveals the importance of serine 1179 in endothelium-dependent vasomotion

Ramona S. Scotland, Manuel Morales-Ruiz, Yan Chen, Jun Yu, Radu Daniel Rudic, David Fulton, Jean Philippe Gratton, William C. Sessa

Research output: Contribution to journalArticle

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Abstract

Phosphorylation of endothelial nitric oxide synthase (eNOS) at serine 1179 can activate the enzyme, leading to NO release. Because eNOS is important in regulating vascular tone, we investigated whether phosphorylation of this residue is involved in vasomotion. Adenoviral transduction of endothelial cells (ECs) with the phosphomimetic S1179DeNOS markedly increased basal and vascular endothelial cell growth factor (VEGF)-stimulated NO release compared with cells transduced with wild-type virus. Conversely, adenoviral transduction of ECs with the nonphosphorylatable S1179AeNOS suppressed basal and stimulated NO release. Using a novel method for luminal delivery of adenovirus, transduction of the endothelium of carotid arteries from eNOS knockout mice with S1179DeNOS completely restored NO-mediated dilatation to acetylcholine (ACh), whereas vasomotor responses in arteries transduced with S1179AeNOS were significantly attenuated. Basal NO release was also significantly reduced in arteries transduced with S1179AeNOS, compared with S1179DeNOS. Thus, our data directly demonstrate that phosphorylation of eNOS at serine 1179 is an important regulator of basal and stimulated NO release in ECs and in intact blood vessels.

Original languageEnglish (US)
Pages (from-to)904-910
Number of pages7
JournalCirculation research
Volume90
Issue number8
DOIs
StatePublished - May 3 2002

Fingerprint

Nitric Oxide Synthase Type III
Serine
Endothelium
Endothelial Cells
Phosphorylation
Blood Vessels
Arteries
Carotid Arteries
Adenoviridae
Knockout Mice
Vascular Endothelial Growth Factor A
Acetylcholine
Dilatation
Viruses
Enzymes

Keywords

  • Adenovirus
  • Endothelium
  • Nitric oxide
  • Signal transduction
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Functional reconstitution of endothelial nitric oxide synthase reveals the importance of serine 1179 in endothelium-dependent vasomotion. / Scotland, Ramona S.; Morales-Ruiz, Manuel; Chen, Yan; Yu, Jun; Rudic, Radu Daniel; Fulton, David; Gratton, Jean Philippe; Sessa, William C.

In: Circulation research, Vol. 90, No. 8, 03.05.2002, p. 904-910.

Research output: Contribution to journalArticle

Scotland, Ramona S. ; Morales-Ruiz, Manuel ; Chen, Yan ; Yu, Jun ; Rudic, Radu Daniel ; Fulton, David ; Gratton, Jean Philippe ; Sessa, William C. / Functional reconstitution of endothelial nitric oxide synthase reveals the importance of serine 1179 in endothelium-dependent vasomotion. In: Circulation research. 2002 ; Vol. 90, No. 8. pp. 904-910.
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