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(Circulation. 2003;107:2475.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Neurovascular Dissociation With Paradoxical Forearm Vasodilation During Systemic Tyramine Administration

Giris Jacob, MD, DSc; Fernando Costa, MD; Simi Vincent, MD, PhD; David Robertson, MD; Italo Biaggioni, MD

From the Jacob Recanati Autonomic Dysfunction Center, Department of Internal Medicine C, Rambam Medical Center, Haifa, Israel (G.J.); the American Heart Association, Dallas, Tex (F.C.); and the Clinical Research Center, Department of Medicine, Pharmacology, and Neurology, Vanderbilt University Medical Center, Nashville, Tenn (S.V., D.R., I.B.).

Correspondence to Italo Biaggioni, MD, Clinical Trials Center, 1500 21st Ave S, Suite 3500, Vanderbilt University, Nashville, TN 37212. E-mail italo.biaggioni{at}vanderbilt.edu

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.

Methods and 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 · dL^-1 · 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 · dL^-1 · 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.

Key Words: nervous system, sympathetic • norepinephrine • blood flow • catecholamines

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