Amine metabolism: A novel path to coronary artery vasospasm

D. J. Conklin, C. L. Boyce, M. B. Trent, P. J. Boor

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

We hypothesized that allylamine (AA) induces subendocardial necrosis in mammals via coronary artery (CA) vasospasm. Additionally, AA toxicity is likely dependent on the enzyme semicarbazide-sensitive amine oxidase (SSAO), which is highly expressed in the aorta of rats and humans. We tested whether AA or acrolein (1, 10, 100, and 1000 μM), a highly reactive product of AA metabolism by SSAO, could contract CA or thoracic aorta (TA) in vitro and if the AA effects involved SSAO. AA or acrolein produced a similar pattern of responses in both CA and TA rings at 100 and 1000 μM, including (1) increased basal tension, (2) enhanced agonist-induced contraction (hypercontractility or vasospasm), (3) remarkable, agonist-induced slow wave vasomotion (vasospasm), and (4) irreversible reduction in vessel contractility after 1 mM exposure. Endothelium-dependent acetylcholine-induced relaxation was not altered during vasospasm in either vessel. Pretreatment with the SSAO inhibitor semicarbazide (1 mM; 10 min) prevented or significantly reduced the majority of AA's effects in both CA and TA rings and inhibited 100% of the SSAO activity present in rat TA and human CA and TA. We propose a two-step model for AA induction of CA vasospasm and resultant myocardial necrosis: (1) metabolism of AA to acrolein by coronary arterial SSAO activity and (2) acrolein induction of CA vasospasm independent of endothelial injury-a novel path.

Original languageEnglish (US)
Pages (from-to)149-159
Number of pages11
JournalToxicology and Applied Pharmacology
Volume175
Issue number2
DOIs
StatePublished - Sep 1 2001

Keywords

  • Allylamine (3-aminopropene)
  • Amine oxidase EC 1.4.3.6
  • Aorta
  • Contraction
  • Human coronary artery disease
  • Hypercontractility
  • Myocardial necrosis
  • Semicarbazide-sensitive amine oxidase
  • Tension oscillations
  • Vascular toxicity
  • Vasomotion
  • Vasospasm

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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