We hypothesized that allylamine (AA) induces subendocardial necrosis in mam
mals via coronary artery (CA) vasospasm. Additionally, AA toxicity is likel
y dependent on the enzyme semicarbazide-sensitive amine oxidase (SSAO), whi
ch is highly expressed in the aorta of rats and humans. We tested whether A
A or acrolein (1, 10, 100, and 1000 muM), a highly reactive product of AA m
etabolism 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 muM, including (1) incre
ased basal tension, (2) enhanced agonist-induced contraction (hypercontract
ility or vasospasm), (3) remarkable, agonist-induced slow wave vasomotion (
vasospasm), and (4) irreversible reduction in vessel contractility after I
mM exposure. Endothelium-dependent acetylcholine-induced relaxation was not
altered during vasospasm in either vessel. Pretreatment with the SSAO inhi
bitor semicarbazide (1 mM; 10 min) prevented or significantly reduced the m
ajority, 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 nove
l path. (C) 2001 Academic Press.