Allylamine and beta-aminopropionitrile-induced vascular injury: an in vivo and in vitro study

Abstract

Toxic cardiovascular effects of allylamine and beta-aminopropionitrile were studied in adult male Sprague-Dawley rats given allylamine alone (AA), 100 mg/kg/day, beta-aminopropionitrile alone (beta APN), 1 g/kg/day, or both chemicals (AA + beta APN) by gavage. Rats were given a total of 10 doses in 11 days. Rats given AA + beta APN 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 + beta APN treatments, but were more numerous and larger in the latter group by morphometric analysis (p less than 0.03). Myocardial necrosis was much less severe in the AA + beta APN treatment group than in rats given only AA. A long-term follow-up (47 and 180 days) after the AA + beta APN 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 beta APN 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 beta APN 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.