Amine metabolism: a novel path to coronary artery vasospasm.
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.
Conklin
D J
DJ
Biology Department, University of Wisconsin-Eau Claire, Eau Claire, Wisconsin 54702-4004, USA.
Boyce
C L
CL
Trent
M B
MB
Boor
P J
PJ
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
D012663:Semicarbazides; C010059:carbamylhydrazine; D000499:Allylamine; D000171:Acrolein; D006631:Amine Oxidase (Copper-Containing)