Circulation, Vol 85, 1775-1785, Copyright © 1992 by American Heart Association
G Eisenhofer, MD Esler, IT Meredith, A Dart, RO Cannon 3d, AA Quyyumi, G Lambert, J Chin, GL Jennings and DS Goldstein
BACKGROUND. Measurement of cardiac norepinephrine spillover may indicate
the amount of transmitter at neuroeffector sites but does not distinguish
neuronal release or reuptake in determining this amount or provide
information about other aspects of sympathetic function. This report
examines how cardiac spillover of the norepinephrine metabolite
dihydroxyphenylglycol (DHPG) provides additional distinct information about
cardiac sympathetic function. METHODS AND RESULTS. Arterial and coronary
venous blood samples were taken during cardiac catheterization and
intravenous infusion of [3H]norepinephrine in 57 subjects. Subjects were
given intravenous yohimbine or underwent mental stress, handgrip exercise,
and cycling exercise to activate sympathetic nerves or were given
intravenous desipramine to block norepinephrine reuptake. Cardiac DHPG
spillover (601 +/- 41 pmol/min) was eightfold greater than norepinephrine
spillover (78 +/- 10 pmol/min) at rest and increased during sympathetic
activation by 65% of the increase of norepinephrine. This and the
desipramine-sensitive cardiac production of [3H]-labeled DHPG from
[3H]norepinephrine indicated that 10.5 times more endogenous norepinephrine
is recaptured than escapes into plasma; that more than 90% of recaptured
norepinephrine is sequestered into storage vesicles; and that under resting
conditions, most cardiac spillover of DHPG and turnover of norepinephrine
are from metabolism of transmitter leaking from vesicles; the latter
process is independent of exocytotic transmitter release with a rate at
rest over 100-fold that of norepinephrine spillover and over 10-fold that
of norepinephrine reuptake. CONCLUSIONS. Cardiac spillover of DHPG provides
information about processes close to or within sympathetic nerve endings
that cannot be provided by measurements of norepinephrine spillover alone.
This includes quantitative information about the role of neuronal uptake in
terminating the actions of norepinephrine at neuroeffector sites and the
importance of vesicular-axoplasmic exchange of norepinephrine as a dynamic
process contributing to norepinephrine turnover.
ARTICLES
Sympathetic nervous function in human heart as assessed by cardiac spillovers of dihydroxyphenylglycol and norepinephrine
Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md. 20892.
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