A dipeptidyl peptidase-4 inhibitor ameliorates hypertensive cardiac remodeling via angiotensin-II/sodium-proton pump exchanger-1 axis.
J Mol Cell Cardiol
; 98: 37-47, 2016 09.
Article
em En
| MEDLINE
| ID: mdl-27374118
ABSTRACT
BACKGROUND:
To address the impact of antidiabetic drugs on cardiovascular safety is a matter of clinical concern. Preclinical studies revealed that various protective effects of dipeptidyl peptidase-4 inhibitor (DPP4i) on cardiovascular disease; however, its impact of on hypertension remains controversial. METHODS ANDRESULTS:
Teneligliptin (TEN; 10mg/kg/day/p.o.) ameliorates hypertension and cardiac remodeling by normalizing a rise of angiotensin-II (AngII) that specifically observed in spontaneously hypertensive rats (SHR). TEN had no effects on vasculature and concentrations of the DPP4-related vasoactive peptides (bradykinin, neuropeptide Y, and atrial natriuretic peptide). The primary action of TEN on BP lowering was due to restoring the AngII-induced manifestation of congestive heart failure observed in SHR. Sodium-proton pump exchanger type 1 (NHE-1) is a regulator of intracellular acidity (pHi) and implicated pathophysiological role in cardiac remodeling occurred in diseased myocardium. Cardiac NHE-1 expression level was increased in SHR and this was restored in TEN-treated SHR. AngII directly augmented cardiac NHE-1 expression and its activity that contributed to hypertrophic response. TEN attenuated the AngII-induced cardiac hypertrophy with decline in pHi via suppression of NHE-1. Loss of NHE-1 activity by specific inhibitor or RNA silencing promoted intracellular acidification and consistently attenuated the AngII-mediated cardiac hypertrophy.CONCLUSION:
The present study revealed the protective actions of TEN on hypertension and comorbid cardiac remodeling via AngII/NHE-1 axis and the novel pathophysiological roles of intracellular acidification via NHE-1 in cardiac hypertrophy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Angiotensina II
/
Trocadores de Sódio-Hidrogênio
/
Remodelação Ventricular
/
Inibidores da Dipeptidil Peptidase IV
/
Hipertensão
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article