This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Eisenhofer, G. Articles by Esler, M. D. Search for Related Content PubMed PubMed Citation Articles by Eisenhofer, G. Articles by Esler, M. D.

Circulation, Vol 84, 1354-1363, Copyright © 1991 by American Heart Association

ARTICLES

Neuronal reuptake of norepinephrine and production of dihydroxyphenylglycol by cardiac sympathetic nerves in the anesthetized dog

G Eisenhofer, JJ Smolich, HS Cox and MD Esler
Baker Medical Research Institute, Prahran, Victoria, Australia.

BACKGROUND. Reuptake of norepinephrine by cardiac sympathetic nerves before and during two levels of electrical stimulation of the left ansa subclavia was estimated in anesthetized dogs from the cardiac production of dihydroxyphenylglycol (DHPG), the intraneuronal metabolite of norepinephrine. METHODS AND RESULTS. The method depended on the effects of neuronal uptake blockade with desipramine on the cardiac production of [3H]DHPG from intravenously infused [3H]norepinephrine. The ratio of the desipramine-induced decrease in the cardiac extraction of [3H]norepinephrine to the production of [3H]DHPG was used to transform the cardiac production of DHPG from recaptured norepinephrine into a rate for norepinephrine reuptake. Cardiac spillover of norepinephrine into plasma increased from 49 +/- 12 to 205 +/- 40 and 451 +/- 118 pmol/min during sympathetic activation. Cardiac DHPG production increased from 108 +/- 18 to 166 +/- 34 and 240 +/- 47 pmol/min. Desipramine decreased resting cardiac DHPG production by 20% and completely blocked the stimulation-induced increase. Thus, most (80%) cardiac DHPG produced at rest was derived from norepinephrine leaking from storage vesicles. This amount remained constant, and that derived from recaptured norepinephrine increased during sympathetic activation. The cardiac extraction of [3H]norepinephrine (126,000 dpm/min) and production of [3H]DHPG (3,790 dpm/min) were decreased by 55-57% after desipramine. Thus, only 3% of the norepinephrine recaptured by cardiac sympathetic nerves appeared in plasma as DHPG. The remainder was sequestered into storage vesicles (more than 94%) or ultimately formed metabolites other than DHPG (less than 3%). Reuptake of norepinephrine by cardiac sympathetic nerves was 1,188 +/- 476 pmol/min and increased in parallel with cardiac norepinephrine spillover to 4,182 +/- 1,982 and 6,594 +/- 2,241 pmol/min during sympathetic stimulation. CONCLUSIONS. Of the norepinephrine released by cardiac sympathetic nerves, 16-fold more was recaptured than entered plasma. Combined estimation of norepinephrine reuptake and spillover offers an approach to assess the efficiency of neuronal reuptake in disorders of cardiac function.

This article has been cited by other articles:

				C. N. Andrews, A. E. Bharucha, M. Camilleri, P. A. Low, B. Seide, D. Burton, K. Baxter, and A. R. Zinsmeister Nitrergic contribution to gastric relaxation induced by glucagon-like peptide-1 (GLP-1) in healthy adults Am J Physiol Gastrointest Liver Physiol, May 1, 2007; 292(5): G1359 - G1365. [Abstract] [Full Text] [PDF]

				G. Eisenhofer, I. J. Kopin, and D. S. Goldstein Catecholamine Metabolism: A Contemporary View with Implications for Physiology and Medicine Pharmacol. Rev., September 1, 2004; 56(3): 331 - 349. [Abstract] [Full Text] [PDF]

				T. Akiyama and T. Yamazaki Myocardial interstitial norepinephrine and dihydroxyphenylglycol levels during ischemia and reperfusion Cardiovasc Res, January 1, 2001; 49(1): 78 - 85. [Abstract] [Full Text] [PDF]

				T. W. Lameris, A. H. van den Meiracker, F. Boomsma, G. Alberts, S. de Zeeuw, D. J. Duncker, P. D. Verdouw, and A. J. M. I.'t Veld Catecholamine handling in the porcine heart: a microdialysis approach Am J Physiol Heart Circ Physiol, October 1, 1999; 277(4): H1562 - H1569. [Abstract] [Full Text] [PDF]

				G. E. Newton, E. R. Azevedo, and J. D. Parker Inotropic and Sympathetic Responses to the Intracoronary Infusion of a ß2-Receptor Agonist : A Human In Vivo Study Circulation, May 11, 1999; 99(18): 2402 - 2407. [Abstract] [Full Text] [PDF]

				A. Mokrane and R. Nadeau Dynamics of heart rate response to sympathetic nerve stimulation Am J Physiol Heart Circ Physiol, September 1, 1998; 275(3): H995 - H1001. [Abstract] [Full Text] [PDF]

				G. Eisenhofer, B. Rundqvist, and P. Friberg Determinants of cardiac tyrosine hydroxylase activity during exercise-induced sympathetic activation in humans Am J Physiol Regulatory Integrative Comp Physiol, March 1, 1998; 274(3): R626 - R634. [Abstract] [Full Text] [PDF]

				G. Eisenhofer, P. Friberg, B. Rundqvist, A. A. Quyyumi, G. Lambert, D. M. Kaye, I. J. Kopin, D. S. Goldstein, and M. D. Esler Cardiac Sympathetic Nerve Function in Congestive Heart Failure Circulation, May 1, 1996; 93(9): 1667 - 1676. [Abstract] [Full Text]