Enhanced prostaglandin synthesis contributes to the venoconstrictor activity of ergotamine.

Spiral strips from dog saphenous veins were contracted by 2.5 X 10(-9) M ergotamine, a concentration giving about 50% of maximal response. Phentolamine (3.6 X 10(-6) M) reduced these effects by 60% and indomethacin (2.8 X 10(-7) M) by 30%. Indomethacin was more effective in reducing ergotamine-induced increase of prostaglandin E-like activity in the bathing fluid than those induced by noradrenaline or potassium chloride. Arachidonic acid was more effective in increasing tension in ergotamine-stimulated than in noradrenaline- or potassium-stimulated veins. These findings suggest that the long-lasting venoconstrictor activity of ergotamine is mediated mainly by alpha-adrenoceptors but that enhanced formation of prostaglandin E-like substance(s) may also contribute.