کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1911014 1046797 2006 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Peroxynitrite and myocardial contractility: In vivo versus in vitro effects
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Peroxynitrite and myocardial contractility: In vivo versus in vitro effects
چکیده انگلیسی

Generation of peroxynitrite (ONOO−) as a result of altered redox balance has been shown to affect cardiac function; however, inconsistencies in the data exist, particularly for myocardial contractility. The hypothesis that the cardiac impact of ONOO− formation depends on its site of generation, intravascular or intramyocardial, was examined. Cardiac contractility was assessed by pressure-volume analysis to delineate vascular versus cardiac changes on direct infusion of ONOO− into the right atria of conscious dogs both with normal cardiac function and in heart failure. Additionally, ONOO− was administered to isolated murine cardiomyocytes to mimic in situ cardiac generation. When infused in vivo, ONOO− had little impact on inotropy but led to systemic arterial dilation, likely as a result of rapid decomposition to NO2− and NO3−. In contrast, infused ONOO− was long lived enough to abolish β-adrenergic (dobutamine)-stimulated contractility/relaxation, most likely through catecholamine oxidation to aminochrome. When administered to isolated murine cardiomyocytes, ONOO− induced a rapid reduction in sarcomere shortening and whole cell calcium transients, although neither decomposed ONOO− or NaNO2 had any effect. Thus, systemic generation of ONOO− is unlikely to have primary cardiac effects, but may modulate cardiac contractile reserve, via blunted β-adrenergic stimulation, and vascular tone, as a result of generation of NO2− and NO3−. However, myocyte generation of ONOO− may impair contractile function by directly altering Ca2+ handling. These data demonstrate that the site of generation within the cardiovascular system largely dictates the ability of ONOO− to directly or indirectly modulate cardiac pump function.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 41, Issue 10, 15 November 2006, Pages 1606–1618
نویسندگان
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