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- Title
Assessment of vasoconstrictive potential of D-lysergic acid using an isolated bovine lateral saphenous vein bioassay<sup>1</sup>.
- Authors
Klotz, J. L.; Bush, L. P.; Smith, D. L.; Shafer, W. D.; Smith, L. L.; Vevoda, A. C.; Craig, A. M.; Arrington, B. C.; Strickland, J. R.
- Abstract
Vasoconstriction has been associated with several symptoms of fescue toxicosis thought to be alkaloid induced. Lysergic acid, an ergot alkaloid, has been proposed as a toxic component of endophyte-infected tall fescue. The objective of this study was to examine the vasoconstrictive potential of D-lysergic acid using a bovine lateral (cranial branch) saphenous vein bioassay. Before testing lysergic acid, validation of the bovine lateral saphenous vein bioassay for use with a multimyograph apparatus was conducted using a dose-response to norepinephrine to evaluate the effects of limb of origin (right vs. left) and overnight storage on vessel contractile response. Segments (2 to 3 cm) of the cranial branch of the lateral saphenous vein were collected from healthy mixed breed cattle (n = 12 and n = 7 for the lysergic acid and norepinephrine experiments, respectively) at local abattoirs. Tissue was placed in modified Krebs-Henseleit, oxygenated buffer and kept on ice or stored at 2 to 8°C until used. Veins were trimmed of excess fat and connective tissue, sliced into 2- to 3-mm sections, and suspended in a myograph chamber containing 5 mL of oxygenated Krebs-Henseleit buffer (95% O2, 5% CO2 pH = 7.4; 37°C). Tissue was allowed to equilibrate at 1 g of tension for 90 mm before initiation of treatment additions. Increasing doses of norepinephrine (1 × 10-8 to 5 × 10-4 M) or lysergic acid (1 × 10-11 to 1 × 10-4 M) were administered every 15 mm after buffer replacement. Data were normalized as a percentage of the contractile response induced by a reference dose of norepinephrine. Veins from both left and right limbs demonstrated contractions in a dose-dependent manner (P < 0.01) but did not differ between limbs. There were no differences in dose-response to norepinephrine between tissue tested the day of dissection and tissue tested 24 h later. Exposure of vein segments to increasing concentrations of lysergic acid did not result in an appreciable contractile response until the addition of 1 × 10-4 M lysergic acid (15.6 ± 2.3% of the 1 × 10-4 M norepinephrine response). These data indicate that only highly elevated concentrations of lysergic acid result in vasoconstriction. Thus, in relation to the symptoms associated with vasoconstriction, lysergic acid may only play a minor role in the manifestation of fescue toxicosis.
- Subjects
ALKALOIDS; BIOLOGICAL assay; LSD (Drug); CATTLE; SLAUGHTERING; NORADRENALINE; EXTREMITIES (Anatomy); FESCUE; VASOCONSTRICTION
- Publication
Journal of Animal Science, 2006, Vol 84, Issue 11, p3167
- ISSN
0021-8812
- Publication type
Article
- DOI
10.2527/jas.2006-038