MODIFICATION OF THE VASOMOTOR ACTIONS OF METHYSERGIDE IN THE FEMORAL ARTERIAL BED OF THE ANAESTHETIZED DOG BY CHANGES IN SYMPATHETIC NERVE ACTIVITY

• 1 Methysergide has been shown to have a remarkably selective vasoconstrictor action in the carotid arterial bed of the anaesthetized dog following intravenous administration. However we have now shown that under conditions which produce sympathetic blockade methysergide will also constrict the femoral arterial bed and the mechanism involved has been investigated.
• 2 Methysergide (10–100 μg/kg i.v.) produced small but variable effects on femoral arterial blood flow in the anaesthetized dog. However following ganglion blockade (mecamylamine 5 mg/kg i.v.), section of the lumbar sympathetic chain between L₄-L₅ or catecholamine depletion with syrosingopine, methysergide consistently caused dose-related decreases in femoral arterial flow which were associated with increases in femoral arterial vascular resistance.
• 3 Intravenous infusion of methysergide (10 μg/kg/min) or 5-hydroxytryptamine (5-HT, 10 μg/kg/min) inhibited the increases in femoral arterial vascular resistance produced by stimulation of the lumbar sympathetic chain by 70% and 44% respectively whilst increases in vascular resistance produced by close intra-arterially administered noradrenaline were potentiated by 25% and 11% respectively.
• 4 Our results show that the vasomotor actions of methysergide in the dog femoral arterial bed are dependent on the degree of sympathetic activity. This suggests that in the dog the post-junctional vasoconstrictor action of methysergide can be masked by a pre-junctional inhibitory effect on sympathetic nerves which may be mediated through stimulation of a specific pre-junctional receptor for 5-HT.