title: Dipeptidyl peptidase IV inhibition improves cardiorenal function in overpacing-induced heart failure.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Laboratory of Physiology, Faculty of Medicine, ULB, Brussels, Belgium.
authors: Nelson
authors: N
authors: Gomez
authors: Karim
authors: K
authors: Touihri
authors: Veerle
authors: V
authors: Matheeussen
authors: Agnès
authors: A
authors: Mendes Da Costa
authors: Maryam
authors: M
authors: Mahmoudabady
authors: Myrielle
authors: M
authors: Mathieu
authors: Lesley
authors: L
authors: Baerts
authors: Aaron
authors: A
authors: Peace
authors: Pascale
authors: P
authors: Lybaert
authors: Simon
authors: S
authors: Scharpé
authors: Ingrid
authors: I
authors: De Meester
authors: Jozef
authors: J
authors: Bartunek
authors: Marc
authors: M
authors: Vanderheyden
authors: Kathleen
authors: K
authors: Mc Entee
mesh_terms: D000818:Animals; D002147:Calmodulin / Q000378:metabolism; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage; D004195:Disease Models, Animal; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D011719:Pyrazines / Q000008:administration & dosage*; D000068900:Sitagliptin Phosphate; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D013552:Swine; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D002147:Calmodulin; D054873:Dipeptidyl-Peptidase IV Inhibitors; D015850:Interleukin-6; D011719:Pyrazines; D019831:Sodium-Calcium Exchanger; D014230:Triazoles; D020097:Natriuretic Peptide, Brain; D018819:Dipeptidyl Peptidase 4; D000068900:Sitagliptin Phosphate