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

• Published in: The journal of clinical endocrinology and metabolism Vol. 91; no. 12; pp. 5069 - 5075
• Main Authors: Birkenfeld, Andreas L., Boschmann, Michael, Moro, Cedric, Adams, Frauke, Heusser, Karsten, Tank, Jens, Diedrich, André, Schroeder, Christoph, Franke, Gabi, Berlan, Michel, Luft, Friedrich C., Lafontan, Max, Jordan, Jens
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.12.2006; Endocrine Society; The Endocrine Society
• Subjects: Adipose Tissue; Adipose Tissue - cytology; Adipose Tissue - drug effects; Adrenergic beta-Antagonists; Adrenergic beta-Antagonists - pharmacology; Adrenergic receptors; Adult; Atrial Natriuretic Factor; Atrial Natriuretic Factor - administration & dosage; Atrial Natriuretic Factor - pharmacology; Atrial Natriuretic Factor - physiology; Atrial natriuretic peptide; Biological and medical sciences; Blood Glucose; Blood Glucose - analysis; Blood pressure; Body mass index; Calorimetry; Calorimetry, Indirect; Carbohydrate metabolism; Cardiology and cardiovascular system; Cardiovascular Physiological Phenomena; Cardiovascular Physiology; Cells, Cultured; Dose-Response Relationship, Drug; EKG; Endocrinopathies; Energy expenditure; Fatty acids; Fatty Acids, Nonesterified; Fatty Acids, Nonesterified - blood; Female; Fundamental and applied biological sciences. Psychology; Glucose; Glucose - metabolism; Glycerol; Glycerol - blood; Glycerol - metabolism; Glycolysis; Heart; Heart rate; Heart Rate - drug effects; Human health and pathology; Humans; Infusions, Intravenous; Insulin; Lactic acid; Life Sciences; Lipid metabolism; Lipid peroxidation; Lipids; Male; Medical sciences; Metabolism; Microdialysis; Muscle, Skeletal - drug effects; Oxidation; Peptides; Propranolol; Propranolol - pharmacology; Pyruvic acid; Receptors, Adrenergic, beta - physiology; Skeletal muscle; Vertebrates: endocrinology; Human; Regulation(control); Natriuretic hormone; Atrial natriuretic peptide; Circulatory system; Metabolism; Endocrinology; β-Adrenergic receptor
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2006-1084

Context: 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 β-adrenergic receptors and ANP. Design: This was a crossover study, conducted 2004–2005. Setting: The study was conducted at an academic clinical research center. Patients: Patients included 10 healthy young male subjects (body mass index 24 ± 1 kg/m2). Intervention: 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. Main Outcome Measures: Venous nonesterified fatty acid, glycerol, glucose, and insulin; and microdialysate glucose, glycerol, lactate, and pyruvate were measured. Results: ANP increased heart rate dose dependently. β-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 β-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.