Published Online
on April 21, 2003

A more recent version of this article appeared on May 20, 2003

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Submitted on November 27, 2002
Revised on January 31, 2003
Accepted on February 4, 2003

Neurovascular Dissociation With Paradoxical Forearm Vasodilation During Systemic Tyramine Administration

Giris Jacob MD, DSc, Fernando Costa MD, Simi Vincent MD, PhD, David Robertson MD, and 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.).

^* To whom correspondence should be addressed. 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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