TY - JOUR

T1 - Sacubitril/valsartan increases postprandial gastrin and cholecystokinin in plasma

AU - Andersen, Ulrik O.

AU - Terzic, Dijana

AU - Albrechtsen, Nicolai Jacob Wewer

AU - Mark, Peter Dall

AU - Plomgaard, Peter

AU - Rehfeld, Jens F.

AU - Gustafsson, Finn

AU - Goetze, Jens P.

PY - 2020

Y1 - 2020

N2 - Aims: Neprilysin degrades natriuretic peptides in circulation and is also suggested to degrade the gut hormones gastrin and cholecystokinin. Neprilysin inhibition has become a therapeutic strategy and thus a regimen in need of further testing in terms of other hormonal axes besides natriuretic peptides. The aim of this study was to examine whether acute inhibition of neprilysin affects meal-induced responses in gastrin and cholecystokinin concentrations in healthy individuals.Methods and results: Nine healthy young men were included in an open-labelled, randomized cross-over clinical trial. The participants received a standardized meal (25 g fat, 26 g protein, 42 g carbohydrate) on two separate days with or without a one-time dosage of sacubitril ((194 mg)/valsartan (206 mg)). Blood pressure, heart rate and blood samples were measured and collected during the experiment. Statistical differences between groups were assessed using area under the curve together with an ANOVA with a Bonferroni post hoc test. Sacubitril/valsartan increased the postprandial plasma concentrations of both gastrin and cholecystokinin (80% (AUC(0-)(270) (min), P = 0.004) and 60% (AUC(0-270) (min), P = 0.003), respectively) compared with the control meal. No significant hemodynamic effects were noted (blood pressure, AUC(0-)(270) (min), P= 0.86, heart rate, AUC(0-)(270) (min), P = 0.96).Conclusion: Our study demonstrates that sacubitril/valsartan increases the postprandial plasma concentrations of gastrin and cholecystokinin in healthy individuals. The results thus suggest that neprilysin-mediated degradation of gastrin and cholecystokinin is physiologically relevant and may have a role in heart failure patients treated with sacubitril/valsartan.

AB - Aims: Neprilysin degrades natriuretic peptides in circulation and is also suggested to degrade the gut hormones gastrin and cholecystokinin. Neprilysin inhibition has become a therapeutic strategy and thus a regimen in need of further testing in terms of other hormonal axes besides natriuretic peptides. The aim of this study was to examine whether acute inhibition of neprilysin affects meal-induced responses in gastrin and cholecystokinin concentrations in healthy individuals.Methods and results: Nine healthy young men were included in an open-labelled, randomized cross-over clinical trial. The participants received a standardized meal (25 g fat, 26 g protein, 42 g carbohydrate) on two separate days with or without a one-time dosage of sacubitril ((194 mg)/valsartan (206 mg)). Blood pressure, heart rate and blood samples were measured and collected during the experiment. Statistical differences between groups were assessed using area under the curve together with an ANOVA with a Bonferroni post hoc test. Sacubitril/valsartan increased the postprandial plasma concentrations of both gastrin and cholecystokinin (80% (AUC(0-)(270) (min), P = 0.004) and 60% (AUC(0-270) (min), P = 0.003), respectively) compared with the control meal. No significant hemodynamic effects were noted (blood pressure, AUC(0-)(270) (min), P= 0.86, heart rate, AUC(0-)(270) (min), P = 0.96).Conclusion: Our study demonstrates that sacubitril/valsartan increases the postprandial plasma concentrations of gastrin and cholecystokinin in healthy individuals. The results thus suggest that neprilysin-mediated degradation of gastrin and cholecystokinin is physiologically relevant and may have a role in heart failure patients treated with sacubitril/valsartan.

KW - heart failure

KW - cholecystokinin

KW - gastrin

KW - natriuretic peptide

KW - sacubitril/valsartan

KW - neprilysin

U2 - 10.1530/EC-19-0563

DO - 10.1530/EC-19-0563

M3 - Journal article

C2 - 32348960

VL - 9

SP - 438

EP - 444

JO - Endocrine Connections

JF - Endocrine Connections

SN - 2049-3614

IS - 5

ER -