RESUMEN
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.