Circulating Concentrations of C-Type Natriuretic Peptides Increase with Sacubitril/Valsartan Treatment in Healthy Young Men
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Circulating Concentrations of C-Type Natriuretic Peptides Increase with Sacubitril/Valsartan Treatment in Healthy Young Men. / Thonsgaard, Simon; Prickett, Timothy C. R.; Hansen, Lasse H.; Albrechtsen, Nicolai J. Wewer; Andersen, Ulrik Ø.; Terzic, Dijana; Plomgaard, Peter; Gustafsson, Finn; Goetze, Jens P.; Mark, Peter D.
In: Clinical Chemistry, Vol. 68, No. 5, 2022, p. 713–720.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Circulating Concentrations of C-Type Natriuretic Peptides Increase with Sacubitril/Valsartan Treatment in Healthy Young Men
AU - Thonsgaard, Simon
AU - Prickett, Timothy C. R.
AU - Hansen, Lasse H.
AU - Albrechtsen, Nicolai J. Wewer
AU - Andersen, Ulrik Ø.
AU - Terzic, Dijana
AU - Plomgaard, Peter
AU - Gustafsson, Finn
AU - Goetze, Jens P.
AU - Mark, Peter D.
PY - 2022
Y1 - 2022
N2 - Background C-type natriuretic peptide (CNP) is a cardioprotective peptide with high affinity for the ectoenzyme neutral endopeptidase (neprilysin). We aimed to determine whether angiotensin receptor-neprilysin inhibitor treatment acutely affects circulating concentrations of bioactive CNP and its molecular amino-terminal precursor (NT-proCNP). Methods We included 9 and 10 healthy young men in 2 randomized crossover trials with sacubitril/valsartan vs control (Trial 1) and sacubitril/valsartan and sitagliptin vs sitagliptin (Trial 2). The participants were randomized to a single dose of sacubitril/valsartan (194/206 mg) or control at the first visit 30 min prior to a standardized meal intake. We obtained blood samples at 12 time points over 5 h and measured plasma concentrations of NT-proCNP in both trials and CNP in Trial 2. Results NT-proCNP concentrations increased 3.5 h after sacubitril/valsartan treatment, and at 4.5 h concentrations were 42% and 65% higher compared with control in Trial 1 and Trial 2, respectively. The total area under the curve (tAUC)(15-270 min) was 22% higher (P = 0.007) in Trial 1 and 17% higher with treatment (P = 0.017) in Trial 2. Concentrations of bioactive CNP followed a similar temporal pattern with an increase of 93% at 4.5 h and a 31% higher tAUC(15-270 min) compared with control (P = 0.001) in Trial 2. Conclusions Sacubitril/valsartan augments circulating concentrations of both bioactive CNP and NT-proCNP in healthy young men. The increase in bioactive CNP is most likely caused by de novo synthesis and secretion rather than diminished breakdown through neprilysin inhibition. ClinicalTrials.gov registration number NCT03717688
AB - Background C-type natriuretic peptide (CNP) is a cardioprotective peptide with high affinity for the ectoenzyme neutral endopeptidase (neprilysin). We aimed to determine whether angiotensin receptor-neprilysin inhibitor treatment acutely affects circulating concentrations of bioactive CNP and its molecular amino-terminal precursor (NT-proCNP). Methods We included 9 and 10 healthy young men in 2 randomized crossover trials with sacubitril/valsartan vs control (Trial 1) and sacubitril/valsartan and sitagliptin vs sitagliptin (Trial 2). The participants were randomized to a single dose of sacubitril/valsartan (194/206 mg) or control at the first visit 30 min prior to a standardized meal intake. We obtained blood samples at 12 time points over 5 h and measured plasma concentrations of NT-proCNP in both trials and CNP in Trial 2. Results NT-proCNP concentrations increased 3.5 h after sacubitril/valsartan treatment, and at 4.5 h concentrations were 42% and 65% higher compared with control in Trial 1 and Trial 2, respectively. The total area under the curve (tAUC)(15-270 min) was 22% higher (P = 0.007) in Trial 1 and 17% higher with treatment (P = 0.017) in Trial 2. Concentrations of bioactive CNP followed a similar temporal pattern with an increase of 93% at 4.5 h and a 31% higher tAUC(15-270 min) compared with control (P = 0.001) in Trial 2. Conclusions Sacubitril/valsartan augments circulating concentrations of both bioactive CNP and NT-proCNP in healthy young men. The increase in bioactive CNP is most likely caused by de novo synthesis and secretion rather than diminished breakdown through neprilysin inhibition. ClinicalTrials.gov registration number NCT03717688
KW - C-type natriuretic peptide
KW - CNP
KW - natriuretic peptides
KW - NT-proCNP
KW - sacubitril
KW - valsartan
KW - NEPRILYSIN INHIBITION
KW - EXPRESSION
KW - ENALAPRIL
KW - RESPONSES
U2 - 10.1093/clinchem/hvac005
DO - 10.1093/clinchem/hvac005
M3 - Journal article
C2 - 35175317
VL - 68
SP - 713
EP - 720
JO - Clinical Chemistry
JF - Clinical Chemistry
SN - 0009-9147
IS - 5
ER -
ID: 299034952