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Dipeptidyl peptidase IV inhibition improves cardiorenal function in overpacing‐induced heart failure
Author(s) -
Gomez Nelson,
Touihri Karim,
Matheeussen Veerle,
Costa Agnès Mendes,
Mahmoudabady Maryam,
Mathieu Myrielle,
Baerts Lesley,
Peace Aaron,
Lybaert Pascale,
Scharpé Simon,
Meester Ingrid,
Bartunek Jozef,
Vanderheyden Marc,
McEntee Kathleen
Publication year - 2012
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1093/eurjhf/hfr146
Subject(s) - sitagliptin , medicine , heart failure , placebo , natriuretic peptide , cardiology , dipeptidyl peptidase 4 , brain natriuretic peptide , sitagliptin phosphate , heart rate , dipeptidyl peptidase 4 inhibitor , hemodynamics , renal function , endocrinology , blood pressure , diabetes mellitus , type 2 diabetes , alternative medicine , metformin , pathology , insulin
Aims Recent studies indicate that brain natriuretic peptide (BNP 1–32 ) may be truncated into BNP 3–32 by dipeptidyl peptidase IV (DPP4) and that BNP 3–32 has reduced biological activities compared with BNP 1–32 . We investigated if DPP4 contributes to the cardiorenal alterations and to the attenuated response to BNP seen in heart failure. Methods and results Haemodynamic and renal assessment was performed in 12 pigs at baseline, 4 weeks after pacing‐induced heart failure, and during BNP infusion. They were randomized to either placebo or treatment with a DPP4 inhibitor, sitagliptin. After 4 weeks of pacing, heart rate was reduced compared with baseline in the sitagliptin group (60 ± 2 vs. 95 ± 16 b.p.m., P < 0.01), and an increase in stroke volume was observed in the sitagliptin group compared with placebo (+24 ± 6% vs. –17 ± 7%, P < 0.01). Glomerular filtration rate declined at week 4 compared with baseline in the placebo group (1.3 ± 0.4 vs. 2.3 ± 0.3 mL/kg/min, P < 0.01) but remained preserved in the sitagliptin group [1.8 ± 0.2 vs. 2.0 ± 0.3 mL/kg/min, P = NS (non‐significant)]. In the sitagliptin group, BNP infusion improved end‐systolic elastance (68 ± 5 vs. 31 ± 4 mmHg/kg/mL, P < 0.05), ventricular–arterial coupling, and mechanical efficiency. Compared with controls ( n = 6), myocardial gene expression of BNP, interleukin‐6, Na + –Ca 2+ exchanger, and calmodulin was up‐regulated in the placebo group, but not in the sitagliptin group. Conclusion In pacing‐induced heart failure, DPP4 inhibition preserves the glomerular filtration rate, modulates stroke volume and heart rate, and potentiates the positive inotropic effect of exogenous BNP at no energy expense.