title: Sympathetic nervous function in human heart as assessed by cardiac spillovers of dihydroxyphenylglycol and norepinephrine.
abstract: 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.
  
  
  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.
authors.affiliation: Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md. 20892.
authors.forename: G
authors.initials: G
authors.lastname: Eisenhofer
authors.forename: M D
authors.initials: MD
authors.lastname: Esler
authors.forename: I T
authors.initials: IT
authors.lastname: Meredith
authors.forename: A
authors.initials: A
authors.lastname: Dart
authors.forename: R O
authors.initials: RO
authors.lastname: Cannon
authors.forename: A A
authors.initials: AA
authors.lastname: Quyyumi
authors.forename: G
authors.initials: G
authors.lastname: Lambert
authors.forename: J
authors.initials: J
authors.lastname: Chin
authors.forename: G L
authors.initials: GL
authors.lastname: Jennings
authors.forename: D S
authors.initials: DS
authors.lastname: Goldstein
mesh_terms: D002303:Cardiac Output, Low / Q000097:blood / Q000378:metabolism / Q000503:physiopathology; D002396:Catechols / Q000097:blood; D003331:Coronary Vessels; D003891:Desipramine / Q000494:pharmacology; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D009994:Osmolar Concentration; D012016:Reference Values; D013564:Sympathetic Nervous System / Q000503:physiopathology*
chemical_list: D002396:Catechols; D008734:Methoxyhydroxyphenylglycol; D003891:Desipramine; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine