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(Circulation. 2008;117:458-461.)
© 2008 American Heart Association, Inc.

Editorial

Genotype and Vascular Phenotype Linked by Catecholamine Systems

David S. Goldstein, MD, PhD

From the Clinical Neurocardiology Section, Clinical Neurosciences Program, Division of Intramural Research, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md.

Correspondence to David S. Goldstein, MD, PhD, Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Dr, MSC-1620, Building 10, Room 6N252, Bethesda, MD 20892-1620. E-mail goldsteind@ninds.nih.gov

Key Words: Editorials • catecholamines • nervous system, sympathetic • norepinephrine • vasoconstriction • veins • tyramine

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
In this issue of Circulation, Fung and coworkers¹ report associations between hand venous responses to the indirectly acting sympathomimetic amine tyramine and single nucleotide polymorphisms (SNPs) of genes encoding particular proteins related to the synthesis, release, reuptake, and metabolism of catecholamines. The importance of these associations lies in their illustrating how genotypic differences may contribute to phenotypic differences in circulatory functions in healthy adults via sympathetic neuroeffector mechanisms. More generally, identification of SNPs related to catecholamine systems may provide insights into the pathophysiology, diagnosis, and treatment of a variety of cardiovascular disorders.²

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To provide perspective about these findings, this editorial compares and contrasts tyramine-induced changes and sympathetic neuroeffector functions; discusses strengths and weaknesses of the dorsal hand vein model; emphasizes the potential of clinical catecholamine neurochemistry to link genotype with cardiovascular phenotype; and conveys a viewpoint on observational versus hypothesis-driven genotyping.

	Comparison and Contrast Between Tyramine-Induced Changes and Sympathetic Neuroeffector Functions

 
Tyramine produces vasoconstriction via release of endogenous norepinephrine, the main neurotransmitter of the sympathetic nervous system mediating cardiovascular responses to stressors. The authors relied on the local vascular actions of tyramine as an indirectly acting sympathomimetic amine to draw inferences about sympathetic neuroeffector functions.

Mechanisms of tyramine-induced norepinephrine release differ in several respects from those of sympathetically mediated norepinephrine release. The Figure depicts some of these differences.

View larger version (23K):   Figure. Mechanisms of sympathetically mediated and tyramine-induced norepinephrine release. NE indicates norepinephrine; TYR, tyramine; AR, aldehyde reductase; VMAT, vesicular monoamine transporter; and MAO, monoamine oxidase.

First, tyramine releases norepinephrine in a calcium-independent manner³ that is not exocytotic,⁴ in . . . [Full Text of this Article]