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Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2014

Open Access 01-12-2014 | Original investigation

DPP-4 inhibitor linagliptin ameliorates cardiovascular injury in salt-sensitive hypertensive rats independently of blood glucose and blood pressure

Authors: Nobutaka Koibuchi, Yu Hasegawa, Tetsuji Katayama, Kensuke Toyama, Ken Uekawa, Daisuke Sueta, Hiroaki Kusaka, MingJie Ma, Takashi Nakagawa, Bowen Lin, Shokei Kim-Mitsuyama

Published in: Cardiovascular Diabetology | Issue 1/2014

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Abstract

Background

It remains to be elucidated whether dipeptidylpeptidase-4 (DPP-4) inhibitor can ameliorate cardiovascular injury in salt-sensitive hypertension. The present study was undertaken to test our hypothesis that linagliptin, a DPP-4 inhibitor, administration initiated after onset of hypertension and cardiac hypertrophy can ameliorate cardiovascular injury in Dahl salt-sensitive hypertensive rats (DS rats).

Methods

High-salt loaded DS rats with established hypertension and cardiac hypertrophy were divided into two groups, and were orally given (1) vehicle or (2) linagliptin (3 mg/kg/day) once a day for 4 weeks, and cardiovascular protective effects of linagliptin in DS rats were evaluated.

Results

Linagliptin did not significantly affect blood pressure and blood glucose levels in DS rats. Linagliptin significantly lessened cardiac hypertrophy in DS rats, as estimated by cardiac weight and echocardiographic parameters. Linagliptin significantly ameliorated cardiac fibrosis, cardiac macrophage infiltration, and coronary arterial remodeling in DS rats. Furthermore, linagliptin significantly mitigated the impairment of vascular function in DS rats, as shown by the improvement of acetylcholine-induced or sodium nitroprusside-induced vascular relaxation by linagliptin. These cardiovascular protective effects of linagliptin were associated with the attenuation of oxidative stress, NADPH oxidase subunits, p67phox and p22 phox, and angiotensin-converting enzyme (ACE).

Conclusions

Our results provided the experimental evidence that linagliptin treatment initiated after the appearance of hypertension and cardiac hypertrophy protected against cardiovascular injury induced by salt-sensitive hypertension, independently of blood pressure and blood glucose. These beneficial effects of linagliptin seem to be attributed to the reduction of oxidative stress and ACE.
Appendix
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Metadata
Title
DPP-4 inhibitor linagliptin ameliorates cardiovascular injury in salt-sensitive hypertensive rats independently of blood glucose and blood pressure
Authors
Nobutaka Koibuchi
Yu Hasegawa
Tetsuji Katayama
Kensuke Toyama
Ken Uekawa
Daisuke Sueta
Hiroaki Kusaka
MingJie Ma
Takashi Nakagawa
Bowen Lin
Shokei Kim-Mitsuyama
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2014
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-014-0157-0

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