The alpha-adrenergic activity of dihydroergotoxine had been studied in both pithed and urethane or pentobarbitone anaesthetized rats. In anaesthetized rats, blood pressure effects varied with the anaesthetic agent: hypotension with urethane, hypertension with pentobarbitone. This latter pressor response was a peripheral effect. In pithed rats, the vasopressor response to dihydroergotoxine was reduced competitively by yohimbine, and non-competitively by nifedipine, but not by prazosin or methysergide, showing that the vasoconstriction is mediated by alpha 2-adrenoceptors. Dihydroergotoxine decreases the tachycardia elicited by stimulation of the cardioaccelerator nerves, this effect being antagonized by yohimbine. It also reduced the pressor response to (-)-phenylephrine. These results indicated that, on the peripheral vascular system of the rat, dihydroergotoxine acts as an alpha 1-adrenoceptor blocker and an alpha 2-adrenoceptor agonist.
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