Comparative toxicity of the cardiovacular toxin allylamine to porcine aortic smooth muscle and endothelial cells

Abstract

This study supports a recent hypothesis that the cardiovascular toxin, allylamine, is toxic to smooth muscle cells of large elastic arteries (aorta). Cultures of the porcine aortic smooth muscle, endothelial, and fibroblastic cells were exposed to varying concentrations of allylamine ranging from 5 μM to 340 μM. Monitored cytotoxic and cytolytic activities demonstrated that final concentrations of 60 μM allylamine decreased cell population viability of smooth muscle cells as much as 50%. Viability decreased approximately linearly with increasing concentrations of allylamine including spontaneous lysing of smooth muscle cells at 90 μM. Endothelial cells were more resistant to lower concentrations of allylamine requiring 90 μM to decrease cell population viability by 50%. In contrast, fibroblastic cells were very resistant to lower concentrations of allylamine. The specific lytic response of these cells in culture, measured by release of [ 3H]thymidine, gave findings parallel to the viability studies, i.e. at 100 μM allylamine smooth muscle cells demonstrated 75% specific lysis while endothelial cells showed 29%. Growth studies of cells surviving an 8-h exposure to allylamine indicate that surviving endothelial cells have better growth characteristics than surviving smooth muscle cells; both cell lines are also apparently injured at concentrations of allylamine much lower than the CT 50. These studies show that of the cellular components of the vascular wall, smooth muscle cells appear to be the most sensitive to the toxic effects of allylamine.