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

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.