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National Institute of Environmental Health Sciences

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Publication Detail

Title: Amine metabolism: a novel path to coronary artery vasospasm.

Authors: Conklin, D J; Boyce, C L; Trent, M B; Boor, P J

Published In Toxicol Appl Pharmacol, (2001 Sep 1)

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 microM), 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 microM, 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.

PubMed ID: 11543647 Exiting the NIEHS site

MeSH Terms: Acrolein/antagonists & inhibitors; Acrolein/toxicity*; Allylamine/antagonists & inhibitors; Allylamine/toxicity*; Amine Oxidase (Copper-Containing)/metabolism*; Analysis of Variance; Animals; Coronary Vasospasm/chemically induced*; Coronary Vasospasm/metabolism; Coronary Vessels/drug effects; Drug Interactions; Humans; Male; Muscle Contraction/drug effects; Muscle, Smooth, Vascular/drug effects*; Muscle, Smooth, Vascular/metabolism; Rats; Rats, Sprague-Dawley; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Semicarbazides/pharmacology*; Thoracic Arteries/drug effects

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