Nitric oxide reversibly inhibits the migration of cultured vascular smooth muscle cells

Rajabrata Sarkar, Eric G. Meinberg, James C. Stanley, R. David Gordon, R Clinton Webb

Research output: Contribution to journalArticle

332 Citations (Scopus)

Abstract

Augmentation of nitric oxide (NO) production in vivo decreases lesions in a variety of models of arterial injury, and inhibition of NO synthase exacerbates experimental intimal lesions. Both vascular smooth muscle cell (VSMC) proliferation and migration contribute to lesion formation. Although NO inhibit VSMC proliferation, its effects on VSMC migration are unknown. To test the hypothesis that NO inhibits VSMC migration independent of inhibition of proliferation, we examined migration of rat aortic VSMCs after wounding of a confluent culture in the presence of chemical donors of NO. Hydroxyurea was used to eliminate any confounding effect of NO on proliferation. Three NO donors, diethylamine NONOate, spermine NONOate, and S-nitrosoglutathione, exhibited concentration-dependent inhibition of both number of migrating VSMCs and maximal distance migrated. Inhibition of migration was also seen with 8-Br-cGMP, suggesting that activation of guanylate cyclase may play a role in mediating the antimigratory effects of NO. Migration resumed after removal of NO donors, as evidenced by an increase in distance migrated. Measurement of VSMC protein synthesis and mitochondrial respiration indicated that inhibition of migration by NO donors was not due to metabolic cytostasis. These findings indicate that NO reversibly inhibits VSMC migration independent of proliferation or cytotoxicity, a novel mechanism by which both endogenous and pharmacological NO may alter vascular pathology.

Original languageEnglish (US)
Pages (from-to)225-230
Number of pages6
JournalCirculation Research
Volume78
Issue number2
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

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Vascular Smooth Muscle
Smooth Muscle Myocytes
Nitric Oxide
Nitric Oxide Donors
Cell Movement
Cell Proliferation
S-Nitrosoglutathione
Cell Migration Inhibition
Tunica Intima
Hydroxyurea
Muscle Proteins
Guanylate Cyclase
Nitric Oxide Synthase
Blood Vessels
Respiration
Pharmacology
Pathology
Wounds and Injuries

Keywords

  • atherosclerosis
  • cell migration
  • nitric oxide

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Nitric oxide reversibly inhibits the migration of cultured vascular smooth muscle cells. / Sarkar, Rajabrata; Meinberg, Eric G.; Stanley, James C.; Gordon, R. David; Webb, R Clinton.

In: Circulation Research, Vol. 78, No. 2, 01.01.1996, p. 225-230.

Research output: Contribution to journalArticle

Sarkar, Rajabrata ; Meinberg, Eric G. ; Stanley, James C. ; Gordon, R. David ; Webb, R Clinton. / Nitric oxide reversibly inhibits the migration of cultured vascular smooth muscle cells. In: Circulation Research. 1996 ; Vol. 78, No. 2. pp. 225-230.
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