Direct evidence for the importance of endothelium-derived nitric oxide in vascular remodeling

Radu Daniel Rudic, Edward G. Shesely, Nobuyo Maeda, Oliver Smithies, Steven S. Segal, William C. Sessa

Research output: Contribution to journalArticle

633 Citations (Scopus)

Abstract

The vascular endothelium mediates the ability of blood vessels to alter their architecture in response to hemodynamic changes; however, the specific endothelial-derived factors that are responsible for vascular remodeling are poorly understood. Here we show that endothelial-derived nitric oxide (NO) is a major endothelial-derived mediator controlling vascular remodeling. In response to external carotid artery ligation, mice with targeted disruption of the endothelial nitric oxide synthase gene (eNOS) did not remodel their ipsilateral common carotid arteries whereas wild-type mice did. Rather, the eNOS mutant mice displayed a paradoxical increase in wall thickness accompanied by a hyperplastic response of the arterial wall. These findings demonstrate a critical role for endogenous NO as a negative regulator of vascular smooth muscle proliferation in response to a remodeling stimulus. Furthermore, our data suggests that a primary defect in the NOS/NO pathway can promote abnormal remodeling and may facilitate pathological changes in vessel wall morphology associated with complex diseases such as hypertension and atherosclerosis.

Original languageEnglish (US)
Pages (from-to)731-736
Number of pages6
JournalJournal of Clinical Investigation
Volume101
Issue number4
DOIs
StatePublished - Feb 15 1998

Fingerprint

Nitric Oxide
Nitric Oxide Synthase Type III
External Carotid Artery
Common Carotid Artery
Vascular Endothelium
Vascular Smooth Muscle
Genes
Ligation
Blood Vessels
Atherosclerosis
Hemodynamics
Hypertension
Vascular Remodeling

Keywords

  • Atherosclerosis
  • Carotid artery
  • Hyperplasty
  • Nitric oxide
  • Proliferation
  • eNOS knockout mice

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Direct evidence for the importance of endothelium-derived nitric oxide in vascular remodeling. / Rudic, Radu Daniel; Shesely, Edward G.; Maeda, Nobuyo; Smithies, Oliver; Segal, Steven S.; Sessa, William C.

In: Journal of Clinical Investigation, Vol. 101, No. 4, 15.02.1998, p. 731-736.

Research output: Contribution to journalArticle

Rudic, Radu Daniel ; Shesely, Edward G. ; Maeda, Nobuyo ; Smithies, Oliver ; Segal, Steven S. ; Sessa, William C. / Direct evidence for the importance of endothelium-derived nitric oxide in vascular remodeling. In: Journal of Clinical Investigation. 1998 ; Vol. 101, No. 4. pp. 731-736.
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