Klotz J L, Kirch B H, Aiken G E, Bush L P, Strickland J R
USDA-ARS, Forage-Animal Production Research Unit, Lexington, KY 40546, USA.
J Anim Sci. 2008 Apr;86(4):1021-8. doi: 10.2527/jas.2007-0576. Epub 2008 Jan 11.
Vasoconstriction is a response associated with consumption of toxic endophyte-infected tall fescue. It is not known if endophyte-produced alkaloids act alone or collectively in mediating the response. Therefore, the objective of this study was to examine the vasoconstrictive potentials of selected ergot alkaloids, individually or in paired combinations, using bovine lateral saphenous veins biopsied from fescue-naïve cattle. Segments (2 to 3 cm) of vein were surgically biopsied from healthy crossbred yearling heifers (n = 22; 330 +/- 8 kg of BW). 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% O(2)/5% CO(2); pH = 7.4; 37 degrees C). Increasing doses of ergovaline, lysergic acid, and N-acetylloline individually or in combination were evaluated. Contractile data were normalized as a percentage of the contractile response induced by a reference dose of norepinephrine (1 x 10(- 4) M). Increasing concentrations of lysergic acid did not result in an appreciable contractile response until the addition of 1 x 10(- 4) M lysergic acid. In contrast, the vascular response to increasing concentrations of ergovaline was apparent at 1 x 10(- 8) M and increased to a maximum of 104.2 +/- 6.0% with the addition of 1 x 10(- 4) M ergovaline. The presence of N-acetylloline did not alter the onset or magnitude of vascular response to either lysergic acid or ergovaline. The presence of 1 x 10(- 5) M lysergic acid with increasing concentrations of N-acetylloline and ergovaline generated an increased contractile response during the initial additions compared with the responses of N-acetylloline and ergovaline alone. In the presence of 1 x 10(- 7) M ergovaline, the contractile response increased with increasing concentrations of N-acetylloline and lysergic acid. Neither N-acetylloline nor lysergic acid elicited an intense contractile response individually (maximum contractile responses of 1.9 +/- 0.3% and 22.6 +/- 4.1%, respectively), suggesting that this was the result of the repetitive addition of 1 x 10(- 7) M ergovaline. These data indicate that ergovaline is a more potent vascular toxicant than lysergic acid or N-acetylloline. The contractile responses of the ergovaline and lysergic acid combinations appeared to differ from the individual dose responses. These data support the possibility that an additive alkaloid exposure effect may exist and should be considered during evaluations of ergot alkaloids.
血管收缩是与食用感染有毒内生菌的高羊茅相关的一种反应。尚不清楚内生菌产生的生物碱是单独作用还是共同作用来介导这种反应。因此，本研究的目的是使用从未接触过高羊茅的牛的外侧隐静脉，单独或成对组合地检测所选麦角生物碱的血管收缩潜力。从健康的杂交一岁小母牛（n = 22；体重330 +/- 8千克）身上手术切取2至3厘米长的静脉段。去除静脉多余的脂肪和结缔组织，切成2至3毫米的切片，悬挂在含有5毫升含氧克雷布斯 - 亨塞尔特缓冲液（95% O₂/5% CO₂；pH = 7.4；37℃）的肌动描记器腔室中。评估了单独或组合使用的麦角新碱、麦角酸和N - 乙酰麦角酰胺的递增剂量。收缩数据以去甲肾上腺素参考剂量（1 x 10⁻⁴ M）诱导的收缩反应的百分比进行标准化。直到加入1 x 10⁻⁴ M麦角酸，麦角酸浓度增加才导致明显的收缩反应。相比之下，血管对递增浓度麦角新碱的反应在1 x 10⁻⁸ M时明显，加入1 x 10⁻⁴ M麦角新碱时增加到最大值104.2 +/- 6.0%。N - 乙酰麦角酰胺的存在并未改变对麦角酸或麦角新碱的血管反应的起始或幅度。与单独的N - 乙酰麦角酰胺和麦角新碱的反应相比，1 x 10⁻⁵ M麦角酸与递增浓度的N - 乙酰麦角酰胺和麦角新碱共同存在时，在最初添加时产生了增强的收缩反应。在1 x 10⁻⁷ M麦角新碱存在的情况下，收缩反应随着N - 乙酰麦角酰胺和麦角酸浓度的增加而增加。单独的N - 乙酰麦角酰胺和麦角酸均未引发强烈的收缩反应（最大收缩反应分别为1.9 +/- 0.3%和22.6 +/- 4.1%），这表明这是重复添加1 x 10⁻⁷ M麦角新碱的结果。这些数据表明，麦角新碱比麦角酸或N - 乙酰麦角酰胺是更强效的血管毒物。麦角新碱和麦角酸组合的收缩反应似乎与单独的剂量反应不同。这些数据支持可能存在生物碱暴露相加效应的可能性，并且在评估麦角生物碱时应予以考虑。
