Neurovascular dissociation with paradoxical forearm vasodilation during systemic tyramine administration.
BACKGROUND
Despite the widespread use of tyramine as a pharmacological tool to assess the effects of norepinephrine release from sympathetic nerve terminals, its vascular effects are not adequately characterized. In particular, previous results indicate that intravenous tyramine produces little if any systemic vasoconstriction, suggesting that tyramine does not cause significant norepinephrine release from sympathetic nerves innervating peripheral vascular beds. To test this hypothesis, we determined the effects of intravenous tyramine on local forearm norepinephrine spillover and vascular resistance.


RESULTS
Seven healthy subjects were studied with systemic and local forearm norepinephrine spillover and forearm blood flow at baseline, during systemic tyramine infusion, and after sympathetic stimulation induced by the cold pressor test. Tyramine infusion caused a significant increase in systemic and forearm norepinephrine spillover. The amount of norepinephrine released into the forearm by tyramine was similar to that caused by cold pressor stimulation, 0.15+/-0.05 versus 0.18+/-0.05 ng x dL(-1) x min(-1). As expected, forearm vascular resistance increased during the cold pressor test, but tyramine produced forearm vasodilation (4.5+/-1 versus -5+/-1 mm Hg x dL(-1) x min(-1), P<0.03) despite the increase in local norepinephrine spillover. In 6 additional subjects, plasma dopamine increased significantly during tyramine administration, from 11+/-3 to 662+/-105 pg/mL.


CONCLUSIONS
Thus, systemic tyramine infusion evokes a significant increase in peripheral norepinephrine spillover, and this, paradoxically, is associated with local vasodilatation rather than vasoconstriction.
Jacob
Giris
G
Jacob Recanati Autonomic Dysfunction Center, Department of Internal Medicine C, Rambam Medical Center, Haifa, Israel.
Costa
Fernando
F
Vincent
Simi
S
Robertson
David
D
Biaggioni
Italo
I
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects / Q000502:physiology; D003080:Cold Temperature; D004298:Dopamine / Q000097:blood; D005542:Forearm / Q000098:blood supply*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D009638:Norepinephrine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D010656:Phenylephrine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D010812:Physical Stimulation; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014439:Tyramine / Q000008:administration & dosage*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014680:Veins / Q000187:drug effects / Q000502:physiology
D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D004298:Dopamine; D009638:Norepinephrine; D014439:Tyramine