Mechanisms of vascular preservation by a novel NO donor following rat carotid artery intimal injury

J. P. Guo, M. M. Panday, P. M. Consigny, A. M. Lefer

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

We studied the effects of a novel organic nitric oxide (NO) donor, 4- hydroxymethyl-furazan-3-carboxylic acid-2-oxide (CAS-1609), in a rat carotid artery intimal injury model. The NO donor, CAS-1609, or its non-NO-donating control compound, 4-hydroxymethyl-furazan-3-carboxylic acid (C-93-4845), was infused intravenously at 30 μg/day. Seven days after injury, carotid artery rings contracted only 56 ± 6 mg to N(G)-nitro-L-arginine methyl ester in C- 93-4845-treated rats, compared with 120 ± 17 mg in CAS-1609-treated rats (P < 0.02), indicating a preservation of endogenous NO release. Improved responses to the endothelium-dependent dilator, acetylcholine, also occurred in injured arteries treated with CAS-1609. Morphometric analysis of injured carotid arteries given the inactive compound showed marked intimal thickening with an intimal-to-medial ratio (I/M) of 0.76 ± 0.02, compared with a significantly lower I/M of 0.32 ± 0.04 (P < 0.01) in injured carotid arteries given CAS-1609. Additionally, CAS-1609 was found to have a concentration-dependent stimulatory effect on cultured rat aortic endothelial cell proliferation (P < 0.01) but an inhibitory effect on platelet-derived growth factor-BB (10 ng/ml)-stimulated rat aortic smooth muscle cell proliferation (P < 0.01). This is the first study to demonstrate that NO plays a dual role in vascular cell proliferation, stimulating endothelial cells but inhibiting smooth muscle cell proliferation. This dual effect of NO on cell proliferation is associated with an in vivo reduction in neointimal thickening and an acceleration of endothelial recovery determined by both anatomic and functional methods.

Original languageEnglish (US)
Pages (from-to)H1122-H1131
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume269
Issue number3 38-3
DOIs
StatePublished - 1995
Externally publishedYes

Keywords

  • endothelial cell proliferation
  • endothelium-derived relaxing factor
  • neointimal thickening
  • smooth muscle cell proliferation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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