Circulation, Vol 78, 41-48, Copyright © 1988 by American Heart Association
DS Goldstein, JE Brush Jr, G Eisenhofer, R Stull and M Esler
Neuronal uptake (Uptake-1) of the sympathetic neurotransmitter
norepinephrine from the circulation in the human heart was assessed in vivo
with three techniques. 1) Cardiac removal of intravenously infused
tracer-labeled norepinephrine was measured before and after Uptake-1
blockade with desipramine; 2) the difference between the fractional
extraction of radioactive norepinephrine and of radioactive isoproterenol,
which is not a substrate for neuronal uptake, was used to estimate the
removal of norepinephrine by Uptake-1 in the heart compared with other
vascular beds (arm, leg, brain, and lungs); and 3) regional arteriovenous
differences in radioactive and endogenous dihydroxyphenylglycol (DHPG), an
exclusively intraneuronal metabolite of norepinephrine, were compared in
these beds. In untreated patients, cardiac removal of radioactive
norepinephrine averaged 79%, whereas in desipramine-treated patients,
cardiac removal of radioactive norepinephrine averaged 19%, a value similar
to that of isoproterenol in untreated patients (14%), confirming that in
the heart the non- neuronal removals of isoproterenol and norepinephrine
were similar. In the heart, 69% of delivered norepinephrine was estimated
to be removed by Uptake-1, a much higher percentage than that in the arm
(14%), leg (7%), brain (10%), and lungs (4%). The cardiac arteriovenous
increment in endogenous DHPG (137%) far exceeded that of the other beds
(49%, 26%, 39%, and -19%, respectively), and radioactive DHPG in the great
cardiac vein exceeded arterial levels by 113%, whereas in the other beds,
arterial radioactive DHPG exceeded venous levels. The results indicate that
the human heart is exceptionally dependent on neuronal uptake for in vivo
removal of circulating norepinephrine.
ARTICLES
In vivo measurement of neuronal uptake of norepinephrine in the human heart
Hypertension-Endocrine Branch, National Heart, Lung, and Blood Institute, Bethesda, MD 20892.
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