The pathophysiologic effects of the alkaloids of tall fescue (Festuca arundinaceae, Schreb,) in cattle

Abstract

Halostachine, a sympathomimetic amine present in tall fescue, was evaluated as a possible contributing agent in the development of fescue toxicity in cattle. A gas chromatographic method was developed for the analysis of halostachine (N-methyl phenylethanolamine) in tall fescue. The recovery of halostachine from spiked plant extract was 66.7 (+OR-) 2%. Halostachine was found to complex with N-formyl and N-acetyl loline in plant extracts. The ratio of free versus conjugated halostachine fluctuated with the concentration of loline alkaloids in the plant. The binding of halostachine to the carbonyl groups of the loline alkaloids was prevented by the addition of hydroxylamine (NH(,2)OH) as NH(,2)OH reacts with the carbonyl groups to form oximes. Recovery of halostachine was not improved, as the oximes were not stable under the pH changes required by the extraction process. The levels of halostachine in a test pasture of Kenhy tall fescue were correlated with the occurrence of signs of fescue toxicity in cattle grazing the pasture. Halostachine content increased prior to an occurrence of an episode of toxicity in December, 1981. The toxicity was also correlated with a period of sustained cold weather. An in vivo study of cattle of the response of blood pressure and coronary band temperature to I.V. administration of racemic halostachine showed that racemic halostachine produced pressor effects (42 mm Hg/0.1 mg/kg) and peripheral vasoconstriction. The pressor effects of halostachine were prevented by an alpha-receptor blocker. Furthermore, tachyphylaxis was not observed. A coronary band temperature decrease also was observed in response to halostachine administration. The administration of an MAO-A inhibitor, norharmane, did not potentiate the effects of halostachine in vivo at a 1 mg/kg dose. An in vitro assay established that halostachine was a substrate for monoamine oxidase (MAO). The K(,m) and V(,max) for beef liver MAO using halostachine as a substrate were 132 (mu)M and 1.13 nM/mg of protein/min, respectively, at 25(DEGREES)C. Norharmane caused a 25% inhibition of the metabolism of halostachine by beef liver MAO at a concentration of 10('-5)M (10 (mu)M). The effect of rumen microflora on halostachine was determined by an in vitro rumen assay. The percentage of halostachine recovered from the active rumen preparations was virtually the same as the amount recovered from the inactive preparations. There was a 10% loss of halostachine probably due to binding of the amine to the organic matter present in the rumen material.