226 Serotonin stimulates relaxation in ovine saphenous vein precontracted with ergovaline

Abstract The predominant ergot alkaloid found in wild type endophyte-infected tall fescue grass is ergovaline. Ergovaline is a potent vasoconstrictor in livestock that consume it. Previous research has shown that ergovaline can bind serotonin (5-HT) receptors and blood vessels exposed to ergovaline become unresponsive to subsequent 5-HT exposure. Serotonin can stimulate vascular contraction or relaxation depending on the receptor subtype targeted. The objective of this experiment was to evaluate 5HT as vasorelaxant in the ovine saphenous artery and vein that were precontracted with ergovaline. Blood vessels were collected from mixed breed market rams (n = 7) at slaughter, cleaned of surrounding adipose and connective tissue, sliced into 2-mm cross-sections, and mounted in a multimyograph. Artery and vein cross-sections were equilibrated to 1 g tension in continuously gassed (95% O2/5% CO2) Krebs-Henseleit buffer (pH 7.4; 37.5 °C) for 90 min, precontracted with 1.0 μM ergovaline (in a tall fescue seed extract) for 30 min, exposed to increasing concentrations of 5-HT that ranged from 1 x 10-9 to 1 x 10-4 M for a 5-min interval. Response data were normalized to the 1.0 μM ergovaline response and were analyzed as a completely randomized design in SAS. The saphenous vein was larger in diameter blood vessel than the saphenous artery. Both vessel types contracted in response to exposure to 1 μM ergovaline. The saphenous artery had a much lower maximal response to ergovaline than did the vein (P < 0.05) that could be attributed to the size difference. The lateral saphenous vein relaxed to increasing concentrations of 5-HT (P < 0.05) with 87 % relaxation occurring by 1 x 10-6 M 5-HT. Conversely, the lateral saphenous artery contracted in response to increasing concentrations of 5-HT (P < 0.05) resulting in a 43% increase from the ergovaline response by the 1 x 10-4 M addition. This response did not become significant in the artery until 1 x 10-5 M 5-HT compared with 1 x 10-8 M for the vein. This resulted in a 50% effective concentration for 5-HT in the artery of 4.5 compared with 8.1 M for the vein (P < 0.05). The differing responses across vessels are likely a result of different receptor populations and this should be verified in future research. This is the first reported observation of stimulated relaxation of a blood vessel constricted ergovaline. Additional research is needed to understand the mechanism of how 5HT can be used to stimulate vasorelaxation in livestock suffering from ergot alkaloid-induced vasoconstriction.