Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1606-1618 |
| Number of pages | 13 |
| Journal | Free Radical Biology and Medicine |
| Volume | 41 |
| Issue number | 10 |
| DOIs | |
| State | Published - Nov 15 2006 |
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Keywords
- Adrenergic (ant)agonists
- Angeli's salt
- Contractile function
- Heart failure
- Isolated myocytes
- Nitric oxide
- Nitroxyl (HNO)
- Peroxynitrite
ASJC Scopus subject areas
- Medicine(all)
- Toxicology
- Clinical Biochemistry
Cite this
Peroxynitrite and myocardial contractility : In vivo versus in vitro effects. / Katori, Tatsuo; Donzelli, Sonia; Tocchetti, Carlo G.; Miranda, Katrina M; Cormaci, Gianfrancesco; Thomas, Douglas D.; Ketner, Elizabeth A.; Lee, Myung Jae; Mancardi, Daniele; Wink, David A.; Kass, David A.; Paolocci, Nazareno.
In: Free Radical Biology and Medicine, Vol. 41, No. 10, 15.11.2006, p. 1606-1618.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Peroxynitrite and myocardial contractility
T2 - In vivo versus in vitro effects
AU - Katori, Tatsuo
AU - Donzelli, Sonia
AU - Tocchetti, Carlo G.
AU - Miranda, Katrina M
AU - Cormaci, Gianfrancesco
AU - Thomas, Douglas D.
AU - Ketner, Elizabeth A.
AU - Lee, Myung Jae
AU - Mancardi, Daniele
AU - Wink, David A.
AU - Kass, David A.
AU - Paolocci, Nazareno
PY - 2006/11/15
Y1 - 2006/11/15
N2 - 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.
AB - 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.
KW - Adrenergic (ant)agonists
KW - Angeli's salt
KW - Contractile function
KW - Heart failure
KW - Isolated myocytes
KW - Nitric oxide
KW - Nitroxyl (HNO)
KW - Peroxynitrite
UR - http://www.scopus.com/inward/record.url?scp=33749659326&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33749659326&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2006.08.023
DO - 10.1016/j.freeradbiomed.2006.08.023
M3 - Article
C2 - 17045928
AN - SCOPUS:33749659326
VL - 41
SP - 1606
EP - 1618
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 10
ER -