Nitric oxide (NO) donor molecules: Effect of NO release rate on vascular smooth muscle cell proliferation in vitro

Daniel L. Mooradian, Thomas C. Hutsell, Larry K. Keefer

Research output: Contribution to journalArticlepeer-review

213 Scopus citations

Abstract

Nitric oxide (NO) inhibits vascular smooth muscle cell (SMC) growth in vitro. To determine the effects of release rate and exposure time on SMC growth inhibition by NO, we compared the activities of five NO donors that generate NO with half-lives of 2 min (DEA/NO, Et2N[N202]Na), 15 min (PAPA/NO, CH3(CH2)2N[N202]-(CH2)3NH3+), 39 min, (SPER/NO, H2N(CH2)3NH2+(CH2)4N[N202]-(CH2)3NH2), 3 h (DPTA/NO, H2N(CH2)4N[N202] (CH2)3NH3+), and 20 h(DETA/NO, H2N(CH2)2N[N202]-(CH2)2NH3+). After 22-h treatment, rat aorta SMC (RA-SMC) DNA synthesis was inhibited with IC50values of 180, 60, and 40 μM for SPER/NO, DPTA/NO, and DETA/NO, respectively. DEA/NO and PAPA/NO did not inhibit DNA synthesis significantly at any concentration tested (20-500 μM). The inhibitory effect of NO on RA-SMC DNA synthesis was thus greatest when a given molar dose of NO was delivered slowly throughout the 22-h period. The antiproliferative effect of DETA/NO was confirmed by measurement of cell numbers for 7 days. When RA-SMC were treated with 500 μM DETA/NO on days 1, 3, and 5, growth was completely suppressed. Cell viability was > 95%, confirming that DETA/NO was not cytotoxic. The results suggest that NO donors may be useful inhibitors of intimal hyperplasia and restenosis after vascular injury such as balloon angioplasty.

Original languageEnglish (US)
Pages (from-to)674-678
Number of pages5
JournalJournal of Cardiovascular Pharmacology
Volume25
Issue number4
DOIs
StatePublished - Apr 1995

Keywords

  • Angioplasty
  • Hyperplasia
  • Nitric oxide
  • Proliferation
  • Restenosis
  • Vascular smooth muscle

Fingerprint

Dive into the research topics of 'Nitric oxide (NO) donor molecules: Effect of NO release rate on vascular smooth muscle cell proliferation in vitro'. Together they form a unique fingerprint.

Cite this