当前位置： SCI文献检索 > JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY期刊下所有文献 > NHE-1 inhibition improves impaired mitochondrial permeability transition and respiratory function during postinfarction remodelling in the rat.

NHE-1 inhibition improves impaired mitochondrial permeability transition and respiratory function during postinfarction remodelling in the rat.

Abstract：

:The mechanism by which Na+-H+ exchange (NHE) inhibition results in attenuation and reversal of postinfarction remodelling and heart failure remains controversial. In this study, we investigated the possible contribution of mitochondrial involvement by determining the effect of the NHE-1-specific inhibitor EMD-87580 (EMD) on mitochondrial permeability transition (MPT) and respiratory function during the postinfarction remodelling process. Male Sprague-Dawley rats were subjected to either 12 or 18 weeks of coronary artery ligation (CAL) or sham procedure. EMD was provided in the diet immediately after ligation. MPT pore opening was determined by perfusing hearts with 2-deoxy-[3H]-glucose ([3H]-DOG) and measurement of mitochondrial [3H]-DOG entrapment. The respiratory function of isolated mitochondria was measured using Clark-type oxygen electrode. Remodelling was associated with significant hypertrophy and there was an increase in MPT pore opening in hearts both 12 and 18 weeks following CAL. Mitochondrial respiratory function, especially state 2 and state 3 rates were significantly decreased in hearts subjected to CAL. EMD suppressed MPT pore opening by 40% (P <0.01) and 35% (P <0.01) 12 and 18 weeks after ligation, respectively. Mitochondria isolated from EMD treated hearts exhibited increased respiratory chain activity for oxidation of substrates at complex I and II. These beneficial effects of EMD were associated with decreased mitochondrial vulnerability to exogenous Ca2+. We conclude that NHE-1 inhibition has a protective effect on mitochondrial function, attenuating MPT pore opening and improving the respiratory function, which may contribute to the salutary effect of NHE-1 inhibitors in heart failure.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Javadov S,Huang C,Kirshenbaum L,Karmazyn M

doi

10.1016/j.yjmcc.2004.10.007

keywords:

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

135-43

issue

1

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(04)00310-4

journal_volume

38

pub_type

杂志文章

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