Assessment of the mitogenic potential of the alkaloids produced by endophyte (Acremonium coenophialum)-infected tall fescue (Festuca arundinacea) on bovine vascular smooth muscle in vitro.
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The objective of these experiments was to test the hypothesis that the major alkaloid classes found in endophyte-infected tall fescue could act as growth promoters for vascular smooth muscle. Bovine vascular smooth muscle cells (VSMC) from the dorsal metatarsal artery were grown in vitro and exposed to five concentrations (10(-6), 10(-8), 10(-9), 10(-11) and 0 M) of ergonovine, alpha-ergocryptine, ergovaline, and N-acetyl loline for 48 h. The mitogenic potential of the alkaloids was tested on both actively growing cells (serum fed, 10% fetal bovine serum) and quiescent cells (serum starved, 0.1% serum) to assess the need for serum constituents for alkaloid induced growth or toxicity. Ergonovine stimulated (P < .07) VSMC growth at 10(-6) M concentration in growing and quiescent culturs and at 10(-8) M concentration in quiescent cultures. alpha-Ergocryptine stimulated (P < .01) growth at 10(-6) M concentration in growing cultures and at 10(-8) and 10(-9) M concentrations in quiescent cultures. Ergovaline exhibited a dual activity on the growth of VSMC in culture, stimulating (P = .06) growth of quiescent cells at 10(-9) M concentration but inhibiting (P < .05) growth of growing cultures at concentrations of 10(-6) and 10(-9) M. This duality of activity was also noted for N-acetyl loline: N-acetyl loline stimulated (P < .05) growth of quiescent cultures at concentrations of 10(-8), 10(-9), and 10(-11) M but inhibited (P < .05) growth of growing cultures at concentrations of 10(-8) and 10(-9) M. The growth effects of the alkaloids in vitro on VSMC support in part the hypothesis that the alkaloids may contribute to the vascular complications noted in cattle grazing endophyte-infected tall fescue through hyperplasia of the intima. This would result in a decreased luminal diameter of the blood vessels and a resultant decrease in blood flow to the afflicted tissues. The diminished blood flow to tissues would result in tissue death and reduced ability to dissipate heat.