Peroxynitrite and myocardial contractility

In vivo versus in vitro effects

Tatsuo Katori, Sonia Donzelli, Carlo G. Tocchetti, Katrina M Miranda, Gianfrancesco Cormaci, Douglas D. Thomas, Elizabeth A. Ketner, Myung Jae Lee, Daniele Mancardi, David A. Wink, David A. Kass, Nazareno Paolocci

Research output: Contribution to journalArticle

45 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1606-1618
Number of pages13
JournalFree Radical Biology and Medicine
Volume41
Issue number10
DOIs
StatePublished - Nov 15 2006

Fingerprint

Peroxynitrous Acid
Cardiac Myocytes
Adrenergic Agents
Blood Vessels
Sarcomeres
Dobutamine
Cardiovascular System
Heart Atria
Muscle Cells
Oxidation-Reduction
Catecholamines
Dilatation
Heart Failure
Dogs
Calcium
Pressure
Cardiovascular system
Pumps
Decomposition
Oxidation

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

Katori, T., Donzelli, S., Tocchetti, C. G., Miranda, K. M., Cormaci, G., Thomas, D. D., ... Paolocci, N. (2006). Peroxynitrite and myocardial contractility: In vivo versus in vitro effects. Free Radical Biology and Medicine, 41(10), 1606-1618. https://doi.org/10.1016/j.freeradbiomed.2006.08.023

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 journalArticle

Katori, T, Donzelli, S, Tocchetti, CG, Miranda, KM, Cormaci, G, Thomas, DD, Ketner, EA, Lee, MJ, Mancardi, D, Wink, DA, Kass, DA & Paolocci, N 2006, 'Peroxynitrite and myocardial contractility: In vivo versus in vitro effects', Free Radical Biology and Medicine, vol. 41, no. 10, pp. 1606-1618. https://doi.org/10.1016/j.freeradbiomed.2006.08.023
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. / Peroxynitrite and myocardial contractility : In vivo versus in vitro effects. In: Free Radical Biology and Medicine. 2006 ; Vol. 41, No. 10. pp. 1606-1618.
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