title: Amine metabolism: a novel path to coronary artery vasospasm.
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.
authors.affiliation: Biology Department, University of Wisconsin-Eau Claire, Eau Claire, Wisconsin 54702-4004, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Conklin
authors.forename: C L
authors.initials: CL
authors.lastname: Boyce
authors.forename: M B
authors.initials: MB
authors.lastname: Trent
authors.forename: P J
authors.initials: PJ
authors.lastname: Boor
mesh_terms: D000171:Acrolein / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000499:Allylamine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D003329:Coronary Vasospasm / Q000139:chemically induced* / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects; D004347:Drug Interactions; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012663:Semicarbazides / Q000494:pharmacology*; D013895:Thoracic Arteries / Q000187:drug effects
chemical_list: D012663:Semicarbazides; C010059:carbamylhydrazine; D000499:Allylamine; D000171:Acrolein; D006631:Amine Oxidase (Copper-Containing)