Beta-adrenergic and atrial natriuretic peptide interactions on human cardiovascular and metabolic regulation.
BACKGROUND
Atrial natriuretic peptide (ANP) has well-known cardiovascular effects and modifies lipid and carbohydrate metabolism in humans.


OBJECTIVE
The objective of the study was to determine the metabolic and cardiovascular interaction of beta-adrenergic receptors and ANP.


METHODS
This was a crossover study, conducted 2004-2005.


METHODS
The study was conducted at an academic clinical research center.


METHODS
PATIENTS included 10 healthy young male subjects (body mass index 24 +/- 1 kg/m2).


METHODS
We infused iv 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, im, and sc microdialysis and indirect calorimetry. Cardiovascular changes were monitored by continuous electrocardiogram and beat-by-beat blood pressure recordings.


METHODS
Venous nonesterified fatty acid, glycerol, glucose, and insulin; and microdialysate glucose, glycerol, lactate, and pyruvate were measured.


RESULTS
ANP increased heart rate dose dependently. beta-Adrenergic receptor blockade abolished the response. ANP elicited a dose-dependent increase in serum nonesterified 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, whereas the lactate to pyruvate ratio decreased, both with and without propranolol. Higher ANP doses increased lipid oxidation, whereas 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.
Birkenfeld
Andreas L
AL
Franz-Volhard Clinical Research Center, Haus 129, Charité Campus Buch, Wiltbergstr. 50, 13125 Berlin, Germany.
Boschmann
Michael
M
Moro
Cedric
C
Adams
Frauke
F
Heusser
Karsten
K
Tank
Jens
J
Diedrich
André
A
Schroeder
Christoph
C
Franke
Gabi
G
Berlan
Michel
M
Luft
Friedrich C
FC
Lafontan
Max
M
Jordan
Jens
J
D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D001786:Blood Glucose / Q000032:analysis; D002153:Calorimetry, Indirect; D002320:Cardiovascular Physiological Phenomena; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000097:blood / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008660:Metabolism; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D011943:Receptors, Adrenergic, beta; D009320:Atrial Natriuretic Factor; D011433:Propranolol; D005947:Glucose; D005990:Glycerol