Tyramine-induced vasodilation mediated by dopamine contamination: a paradox resolved.
We reported previously that intravenous administration of tyramine induced a paradoxical forearm vasodilation and an increase in plasma dopamine, raising the possibility that dopamine is released by or converted from tyramine in vivo. Alternatively, tyramine can be nonenzymatically oxidized into dopamine in vitro, and this contamination may be responsible for the increase in plasma dopamine and forearm vasodilation. To distinguish between these possibilities, we measured the hemodynamic and neurohumoral effects of an intravenous infusion of a specially prepared dopamine-free tyramine solution in 8 normal volunteers at a dose that increased systolic blood pressure by approximately 25 mm Hg (from 107+/-5 to 133+/-5 mm Hg; P <0.001) and compared it with an equivalent dose of norepinephrine. Tyramine increased plasma norepinephrine (139+/-18 to 226+/-30 pg/mL; P <0.02), its intraneuronal metabolite dihydroxyphenylglycol (980+/-73 to 2245+/-206 pg/mL; P <0.001), and systemic vascular resistance, but not plasma dopamine or its intraneuronal metabolite dihydroxyphenylacetic acid. Tyramine and norepinephrine produced nonsignificant increases in forearm vascular resistance. We conclude that tyramine-induced forearm vasodilation reported in previous studies is explained by the presence of dopamine contamination in tyramine preparations. Intravenous administration of dopamine-free tyramine and norepinephrine produced equivalent systemic vasoconstriction. The forearm vasculature was not useful in monitoring the vasoconstrictive effects of either agent. The possibility of dopamine contamination needs to be considered when interpreting previously published studies using tyramine as a pharmacological tool to assess sympathetic function, and it must be avoided in future studies.
Jacob
Giris
G
Jacob Recanati Autonomic Dysfunction Center, Department of Internal Medicine C, Rambam Medical Center, Haifa, Israel.
Gamboa
Alfredo
A
Diedrich
André
A
Shibao
Cyndya
C
Robertson
David
D
Biaggioni
Italo
I
D000328:Adult; D004298:Dopamine / Q000032:analysis* / Q000097:blood; D004340:Drug Contamination; D005542:Forearm / Q000098:blood supply; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D009638:Norepinephrine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D014439:Tyramine / Q000008:administration & dosage* / Q000737:chemistry* / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D014664:Vasodilation
D014662:Vasoconstrictor Agents; D004298:Dopamine; D009638:Norepinephrine; D014439:Tyramine