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This version published online on September 19, 2006
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-1084
A more recent version of this article appeared on December 1, 2006
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Submitted on May 18, 2006
Accepted on September 7, 2006

Beta-Adrenergic and Atrial Natriuretic Peptide Interactions on Human Cardiovascular and Metabolic Regulation

Andreas L. Birkenfeld, Michael Boschmann, Cedric Moro, Frauke Adams, Karsten Heusser, Jens Tank, André Diedrich, Christoph Schroeder, Gabi Franke, Michel Berlan, Friedrich C. Luft, Max Lafontan, and Jens Jordan*

Franz-Volhard Clinical Research Center, Charité - Campus Buch and HELIOS Klinikum, Berlin, Germany; Inserm Unit 586, Institut Louis Bugnard, Université Paul Sabatier, Hôpital Rangueil, Toulouse, France; Autonomic Dysfunction Center, Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical School, Nashville, Tennesse, USA

* To whom correspondence should be addressed. E-mail: jordan{at}fvk.charite-buch.de.

Context: Atrial natriuretic peptide (ANP) has well known cardiovascular effects and modifies lipid and carbohydrate metabolism in humans.

Objective: To determine the metabolic and cardiovascular interaction of {beta}-adrenergic receptors and ANP.

Design: Cross over study, conducted 2004-2005

Setting: Academic clinical research center

Patients: Ten healthy, young, male subjects (BMI 24 ± 1 kg/m2)

Intervention: We infused intravenously incremental ANP doses (6.25, 12.5, and 25 ng/kg/min) with and without propranolol (0.20 mg/kg in divided doses followed by 0.033 mg/kg/h infusion). Metabolism was monitored through venous blood sampling, intramuscular and sc microdialysis and indirect calorimetry. Cardiovascular changes where monitored by continuous ECG and beat-by-beat blood pressure recordings.

Main outcome measures: Venous NEFA, glycerol, glucose, insulin; microdialysate glucose, glycerol, lactate, pyruvate.

Results: ANP increased heart rate dose dependently. {beta}-adrenergic receptor blockade abolished the response. ANP elicited a dose-dependent increase in serum non-esterified fatty acid and glycerol concentrations. The response was not suppressed with propranolol. Venous glucose and insulin concentrations increased with ANP, both, without or with propranolol. ANP induced lipid mobilization in sc adipose tissue. In skeletal muscle, microdialysate lactate increased while the lactate to pyruvate ratio decreased, both, with and without propranolol. Higher ANP doses increased lipid oxidation while energy expenditure remained unchanged. Propranolol tended to attenuate the increase in lipid oxidation.

Conclusions: Selected cardiovascular ANP effects are at least partly mediated by {beta}-adrenergic receptor stimulation. ANP induced changes in lipid mobilization and glycolysis are mediated by another mechanism, presumably stimulation of natriuretic peptide receptors whereas substrate oxidation might be modulated through adrenergic mechanisms.




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