Preserved norepinephrine reuptake but reduced sympathetic nerve endings in hypertrophic volume-overloaded rat hearts.
BACKGROUND
In congestive heart failure (CHF), an activation of the cardiac sympathetic nervous system results in depleted cardiac norepinephrine (NE) stores. The underlying regulatory mechanisms are discussed controversially and were investigated in the present study in CHF resulting from volume overload.


RESULTS
Aorto-caval shunt (AVS) was performed in rats. Plasma NE levels were determined by radioenzymatic assay, left ventricular NE by high-performance liquid chromatography, endothelin-1 by enzyme-linked immunosorbent assay. Tyrosine-hydroxylase (TH)- and nerve growth factor (NGF)-mRNA was determined by Northern blot analysis and ribonuclease-assay. Cardiac [3H]-NE uptake was measured in isolated perfused hearts. Glyoxylic acid-induced histofluorescence was used to quantify cardiac sympathetic nerves. Compared with sham-operated animals (SH), AVS rats were characterized by depleted cardiac NE stores and enhanced NE plasma levels. Neither TH-mRNA levels in stellate ganglia, nor cardiac [3H]-NE-uptake were reduced in AVS. The left ventricular density of sympathetic nerves was markedly decreased. Gene expression of myocardial NGF (a positive regulator of NE reuptake and cardiac sympathetic nerve density) and left ventricular endothelin-1 (a negative regulator of NE reuptake and positive regulator of cardiac NGF expression) were unchanged.


CONCLUSIONS
In volume-overloaded hypertrophic hearts, depletion of cardiac NE stores is caused by a reduction of the sympathetic nerve density, whereas cardiac NE reuptake is preserved.
Kristen
Arnt V
AV
Department of Cardiology, Medical University of Heidelberg, Heidelberg, Germany.
Kreusser
Michael M
MM
Lehmann
Lorenz
L
Kinscherf
Ralf
R
Katus
Hugo A
HA
Haass
Markus
M
Backs
Johannes
J
D000818:Animals; D001011:Aorta / Q000601:surgery; D001166:Arteriovenous Shunt, Surgical; D006332:Cardiomegaly / Q000209:etiology; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D006706:Homeostasis; D006973:Hypertension / Q000150:complications*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009411:Nerve Endings / Q000473:pathology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000473:pathology*; D014684:Venae Cavae
D009638:Norepinephrine