Toxic cardiovascular effects of allylamine and β-aminopropionitrile were studied in adult male Sprague-Dawley rats given allylamine alone (AA), 100 mg/kg/day, β-aminopropionitrile alone (βAPN), 1 g/kg/day, or both chemicals (AA + βAPN) by gavage. Rats were given a total of 10 doses in 11 days. Rats given AA + βAPN showed extensive smooth muscle cell necrosis of the aortic media not seen when either toxin was given alone. Lingual artery lesions in the form of small intracellular eosinophilic globules were seen in animals given AA and AA + βAPN treatments, but were more numerous and larger in the latter group by morphometric analysis (p < 0.03). Myocardial necrosis was much less severe in the AA + βAPN treatment group than in rats given only AA. A long-term follow-up (47 and 180 days) after the AA + βAPN protocol above showed that rats had persistent aortic medial necrosis with striking intimal cartilaginous metaplasia. Cultured porcine aortic smooth muscle cells exposed in vitro to combined AA and βAPN showed markedly decreased viability and increased cell injury when compared to cells exposed to only one toxin, thus supporting the synergistic toxic effect seen in vivo. Our studies show a synergistic necrotizing effect of AA and βAPN on aortic vascular smooth muscle cells. A hypothesis concerning these compounds' effects on vascular amine oxidases is made to explain this toxic synergism. Synergistic toxic interactions may be important in other forms of vascular injury.
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