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 journalArticlepeer-review

710 Scopus citations


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
Issue number4
StatePublished - Feb 15 1998
Externally publishedYes


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

ASJC Scopus subject areas

  • Medicine(all)


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