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. 2025 Jan 4:103:skaf108.
doi: 10.1093/jas/skaf108.

Serotonin can stimulate vasorelaxation in ovine lateral saphenous veins precontracted with ergovaline

James L Klotz  1 , Celina M Checura  2 , Maslyn A Greene  3 , Huihua Ji  4 , Susan K Duckett  3
Affiliations

Serotonin can stimulate vasorelaxation in ovine lateral saphenous veins precontracted with ergovaline

James L Klotz et al. J Anim Sci. .

Abstract

The ergot alkaloid ergovaline is a potent vasoconstrictor. Previous research has shown that ergovaline can bind serotonin (5-HT) receptors and elicit vasoconstrictive activity. Three experiments were conducted to evaluate 5-HT as a vasorelaxant in the ovine saphenous artery and vein. Blood vessels were collected from mixed-breed market ram lambs (n = 23) at slaughter. Experiment 1: artery and vein cross-sections were precontracted with 1 × 10-4 M phenylephrine in a multimyograph for 15 min, exposed to concentrations of 5-HT that ranged from 1 × 10-9 to 1 × 10-4 M for a 5-min interval. Response data were normalized to the 1 × 10-4 M phenylephrine response and were analyzed as a completely randomized design in SAS. The lateral saphenous vein (n = 5 lambs) relaxed to increasing concentrations of 5-HT (P < 0.05) with 65% to 75 % relaxation occurring at 1 × 10-7 M through 1 × 10-4 5-HT. Conversely, the lateral saphenous artery (n = 6 lambs) contracted in response to increasing concentrations of 5-HT (P < 0.05) resulting in a 255% increase from the phenylephrine response by the 1 × 10-4 M addition. Experiment 2: saphenous veins from lambs (n = 5) were exposed to increasing concentrations of selective 5-HT receptor agonists to determine the receptor subtypes involved in the previously observed vasorelaxation. Agonists for receptors 5-HT2B, 5-HT4, and 5-HT7 were used. While all three 5-HT receptor subtypes resulted in vasorelaxation (P < 0.05), the 5-HT2B agonist only stimulated a maximal relaxation of 32% compared to the agonists for 5-HT4 and 5-HT7 that resulted in maximal relaxation of 68% and 50%, respectively. Experiment 3: saphenous arteries and veins were collected from market rams (n = 7) and precontracted with 1 × 10-6 M ergovaline for 30 min. The lateral saphenous vein relaxed to increasing concentrations of 5-HT (P < 0.05) with 87 % relaxation occurring by 1 × 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 × 10-4 M addition. This is the first reported direct observation of stimulated relaxation of a blood vessel constricted by ergovaline. The agonist for 5-HT4 produced the greatest relaxation in the ovine lateral saphenous vein. Serotonin receptors involved in 5-HT-mediated vasorelaxation do not appear to be antagonized by ergovaline and should be targeted in subsequent research focused on mitigation of ergot alkaloid-induced vasoconstriction.

Keywords: ergovaline; serotonin; sheep; vasorelaxation.

Plain language summary

Ergot alkaloids are toxins that can be found in forages and cereal grains that livestock consume. Livestock exposed to these toxins can develop an illness generally referred to as ergotism. Ergot alkaloids can also bind to serotonin receptors disrupting their normal function. One symptom of ergotism associated with serotonin receptor interference is chronic vasoconstriction. This study sought to understand how serotonin regulates vascular tone in sheep lateral saphenous veins and arteries and how this is influenced by the ergot alkaloid ergovaline. Blood vessels were precontracted with a chemical that causes vasoconstriction and it was found that serotonin caused a further contraction in the artery, but resulted in substantial relaxation in the vein. This relaxation also occurred when veins were precontracted with the ergot alkaloid ergovaline. One specific serotonin receptor was identified as responsible for this relaxation and its function was not influenced by the presence of ergovaline. This is the first report of direct observation of relaxation of a blood vessel that was constricted by ergovaline. This work has the potential to lead to mitigation solutions for fescue toxicosis and many different forms of ergotism around the world.

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