Antagonism by methysergide of neurogenic vasoconstriction in the dog forelimb.
In the flow-regulated dog forelimb, electrical stimulation of the efferent median nerve produced frequency-dependent increases in perfusion pressure. These vasoconstrictor effects were attenuated by a large dose of phentolamine, an alpha 1 and alpha 2 blocking drug. Administration of methysergide after phentolamine completely reversed the vasoconstrictor responses to vasodilation at most frequencies of stimulation. In the absence of phentolamine pretreatment, even a lower dose of methysergide reversed or caused biphasic responses (attenuated constriction followed by dilatation) during the nerve stimulation at the lower frequencies (0.5-4.0 Hz). This lower dose of methysergide completely abolished vascular effects of exogenous 5-hydroxytryptamine (5-HT) and potentiated those of norepinephrine; hence, the antagonism by methysergide of neurally mediated vasoconstriction is not caused by an action on alpha-adrenergic receptors. Unlike methysergide, selective 5-HT2 antagonists ketanserin and ritanserin have no modifying effect on exogenous 5-HT responses. These studies have provided pharmacological evidence that suggests that 5-HT may be the neurotransmitter mediating neurogenic vasoconstriction in the dog forelimb, and that this effect does not involve activation of 5-HT2 receptors.
D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D005552:Forelimb / Q000098:blood supply / Q000294:innervation; D007650:Ketanserin / Q000494:pharmacology; D008475:Median Nerve / Q000502:physiology*; D008784:Methysergide / Q000494:pharmacology*; D010646:Phentolamine / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000502:physiology; D016713:Ritanserin; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D016713:Ritanserin; D012701:Serotonin; D007650:Ketanserin; D008784:Methysergide; D010646:Phentolamine