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Dipeptidyl peptidase IV inhibition improves cardiorenal function in overpacing-induced heart failure.
MedLine Citation:
PMID:  22045924     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Nelson Gomez; Karim Touihri; Veerle Matheeussen; Agnès Mendes Da Costa; Maryam Mahmoudabady; Myrielle Mathieu; Lesley Baerts; Aaron Peace; Pascale Lybaert; Simon Scharpé; Ingrid De Meester; Jozef Bartunek; Marc Vanderheyden; Kathleen Mc Entee
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-1
Journal Detail:
Title:  European journal of heart failure     Volume:  -     ISSN:  1879-0844     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100887595     Medline TA:  Eur J Heart Fail     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratory of Physiology, Faculty of Medicine, ULB, Brussels, Belgium.
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