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Am J Physiol Regul Integr Comp Physiol 295: R857-R863, 2008. First published June 18, 2008; doi:10.1152/ajpregu.00190.2008
0363-6119/08 $8.00
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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Cardiac norepinephrine transporter protein expression is inversely correlated to chamber norepinephrine content

Erica A. Wehrwein,1 Lindsay M. Parker,1 Anna A. Wright,1 John M. Spitsbergen,2 Martin Novotny,3 Dagmar Babankova,3 Greg M. Swain,3 Beth A. Habecker,4 and David L. Kreulen1

1Department of Physiology, Michigan State University, East Lansing; 2Department of Biological Sciences, Western Michigan University, Kalamazoo; and 3Department of Chemistry and Neuroscience Program, Michigan State University, East Lansing, Michigan; and 4Department of Physiology and Pharmacology, Oregon Health and Sciences University, Portland, Oregon

Submitted 14 March 2008 ; accepted in final form 11 June 2008

The cardiac neuronal norepinephrine (NE) transporter (NET) in sympathetic neurons is responsible for uptake of released NE from the neuroeffector junction. The purpose of this study was to assess the chamber distribution of cardiac NET protein measured using [3H]nisoxetine binding in rat heart membranes and to correlate NE content to NET amount. In whole mounts of atria, NET was colocalized in nerve fibers with tyrosine hydroxylase (TH) immunoreactivity. NE content expressed as micrograms NE per gram tissue was lowest in the ventricles; however, NET binding was significantly higher in the left ventricle than the right ventricle and atria (P < 0.05), resulting in a significant negative correlation (r2 = 0.922; P < 0.05) of NET to NE content. The neurotoxin 6-hydroxydopamine, an NET substrate, reduced NE content more in the ventricles than the atria, demonstrating functional significance of high ventricular NET binding. In summary, there is a ventricular predominance of NET binding that corresponds to a high NE reuptake capacity in the ventricles, yet negatively correlates to tissue NE content.

reuptake; 6-hydroxydopamine; stellate ganglia; noradrenaline



Address for reprint requests and other correspondence: D. L. Kreulen, 2201 BPS, Dept. of Physiology, Michigan State Univ., East Lansing, MI 48823 (e-mail: dkreulen{at}msu.edu)







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