TY - JOUR
T1 - High doses of ANP and BNP exacerbate lipolysis in humans and the lipolytic effect of BNP is associated with cardiac triglyceride content in pigs
AU - Bartels, Emil D
AU - Guo, Song
AU - Kousholt, Birgitte S
AU - Larsen, Jens R
AU - Hasenkam, J Michael
AU - Burnett, John
AU - Nielsen, Lars B
AU - Ashina, Messoud
AU - Goetze, Jens P
N1 - Copyright © 2018 Elsevier Inc. All rights reserved.
PY - 2019
Y1 - 2019
N2 - Drugs facilitating the cardioprotective effects of natriuretic peptides are introduced in heart failure treatment. ANP and BNP also stimulate lipolysis and increase circulating concentrations of free fatty acids (FFAs); an aspect, however, thought to be confined to primates. We examined the lipolytic effect of natriuretic peptide infusion in healthy young men and evaluated the effect in a porcine model of myocardial ischemia and reperfusion. Six young healthy normotensive men underwent infusion with ANP, BNP, or CNP for 20 min. Blood samples were collected before, during, and after infusion for measurement of FFAs. In a porcine model of myocardial ischemia and reperfusion, animals were infused for 3 h with either BNP (n = 7) or saline (n = 5). Blood samples were collected throughout the infusion period, and cardiac tissue was obtained after infusion for lipid analysis. In humans, ANP infusion dose-dependently increased the FFA concentration in plasma 2.5-10-fold (baseline vs. 0.05 μg/kg/min P < 0.002) and with BNP 1.6-3.5-fold (P = 0.001, baseline vs. 0.02 μg/kg/min) 30 min after initiation of infusion. Infusion of CNP did not affect plasma FFA. In pigs, BNP infusion induced a 3.5-fold increase in plasma FFA (P < 0.0001), which remained elevated throughout the infusion period. Triglyceride content in porcine right cardiac ventricle tissue increased ∼5.5 fold in animals infused with BNP (P = 0.02). Natriuretic peptide infusion has similar lipolytic activity in human and pig. Our data suggest that short-term infusion increases the cardiac lipid content, and that the pig is a suitable model for studies of long-term effects mediated by natriuretic peptides.
AB - Drugs facilitating the cardioprotective effects of natriuretic peptides are introduced in heart failure treatment. ANP and BNP also stimulate lipolysis and increase circulating concentrations of free fatty acids (FFAs); an aspect, however, thought to be confined to primates. We examined the lipolytic effect of natriuretic peptide infusion in healthy young men and evaluated the effect in a porcine model of myocardial ischemia and reperfusion. Six young healthy normotensive men underwent infusion with ANP, BNP, or CNP for 20 min. Blood samples were collected before, during, and after infusion for measurement of FFAs. In a porcine model of myocardial ischemia and reperfusion, animals were infused for 3 h with either BNP (n = 7) or saline (n = 5). Blood samples were collected throughout the infusion period, and cardiac tissue was obtained after infusion for lipid analysis. In humans, ANP infusion dose-dependently increased the FFA concentration in plasma 2.5-10-fold (baseline vs. 0.05 μg/kg/min P < 0.002) and with BNP 1.6-3.5-fold (P = 0.001, baseline vs. 0.02 μg/kg/min) 30 min after initiation of infusion. Infusion of CNP did not affect plasma FFA. In pigs, BNP infusion induced a 3.5-fold increase in plasma FFA (P < 0.0001), which remained elevated throughout the infusion period. Triglyceride content in porcine right cardiac ventricle tissue increased ∼5.5 fold in animals infused with BNP (P = 0.02). Natriuretic peptide infusion has similar lipolytic activity in human and pig. Our data suggest that short-term infusion increases the cardiac lipid content, and that the pig is a suitable model for studies of long-term effects mediated by natriuretic peptides.
KW - Free fatty acids
KW - Lipolysis
KW - Natriuretic peptides
KW - Sus scrofa/metabolism
KW - Natriuretic Peptide, Brain/administration & dosage
KW - Humans
KW - Atrial Natriuretic Factor/administration & dosage
KW - Triglycerides/metabolism
KW - Fatty Acids, Nonesterified/blood
KW - Male
KW - Animals
KW - Myocardial Ischemia/metabolism
KW - Heart/drug effects
KW - Myocardium/metabolism
KW - Female
KW - Models, Animal
KW - Infusions, Intravenous
KW - Disease Models, Animal
UR - http://www.scopus.com/inward/record.url?scp=85057841277&partnerID=8YFLogxK
U2 - 10.1016/j.peptides.2018.11.003
DO - 10.1016/j.peptides.2018.11.003
M3 - Journal article
C2 - 30508635
SN - 0196-9781
VL - 112
SP - 43
EP - 47
JO - Peptides
JF - Peptides
ER -