Enhanced NO and superoxide generation in dysfunctional hearts from endotoxemic rats

Fadi H. Khadour, Donna Panas, P. Ferdinándy, Costas Schulze, T. Csont, Manoj M. Lalu, Stephen M. Wildhirt, Richard Schulz

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Free radicals have been implicated in the etiology of cardiac dysfunction during sepsis, but the actual species responsible remains unclear. We studied the alterations in myocardial nitric oxide (NO), superoxide, and peroxynitrite generation along with cardiac mechanical function and efficiency in hearts from lipopolysaccharide (LPS)-treated rats. Six hours after LPS (4 mg/kg ip) or saline (control) treatment, hearts were isolated and perfused for 1 h with recirculating Krebs-Henseleit buffer and paced at 300 beats/min. Cardiac work, O2 consumption, and cardiac efficiency were markedly depressed in LPS hearts compared with controls. Plasma nitrate/nitrite level was elevated in LPS rats, and ventricular NO production was enhanced as measured by electron spin resonance spectroscopy, Ca2+-independent NO synthase (NOS) activity, and inducible NOS immunohistochemistry. Ventricular superoxide production was also enhanced in LPS-treated hearts as seen by lucigenin chemiluminescence and xanthine oxidase activity. Increased nitrotyrosine staining (immunohistochemistry) and higher lipid hydroperoxides levels were also detected in LPS-treated hearts, indicating oxygen radical-induced stress. Enhanced generation of both NO and superoxide, and thus peroxynitrite, occur in dysfunctional hearts from endotoxemic rats.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume283
Issue number3 52-3
Publication statusPublished - 2002

Fingerprint

Superoxides
Lipopolysaccharides
Nitric Oxide
Peroxynitrous Acid
Immunohistochemistry
Xanthine Oxidase
Lipid Peroxides
Electron Spin Resonance Spectroscopy
Nitric Oxide Synthase Type II
Nitrites
Luminescence
Nitric Oxide Synthase
Nitrates
Free Radicals
Reactive Oxygen Species
Sepsis
Staining and Labeling

Keywords

  • Cardiac dysfunction
  • Nitric oxide
  • Sepsis
  • Superoxide and peroxynitrite

ASJC Scopus subject areas

  • Physiology

Cite this

Enhanced NO and superoxide generation in dysfunctional hearts from endotoxemic rats. / Khadour, Fadi H.; Panas, Donna; Ferdinándy, P.; Schulze, Costas; Csont, T.; Lalu, Manoj M.; Wildhirt, Stephen M.; Schulz, Richard.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 283, No. 3 52-3, 2002.

Research output: Contribution to journalArticle

Khadour, Fadi H. ; Panas, Donna ; Ferdinándy, P. ; Schulze, Costas ; Csont, T. ; Lalu, Manoj M. ; Wildhirt, Stephen M. ; Schulz, Richard. / Enhanced NO and superoxide generation in dysfunctional hearts from endotoxemic rats. In: American Journal of Physiology - Heart and Circulatory Physiology. 2002 ; Vol. 283, No. 3 52-3.
@article{6af9139d765e4df49304a7aa30596f95,
title = "Enhanced NO and superoxide generation in dysfunctional hearts from endotoxemic rats",
abstract = "Free radicals have been implicated in the etiology of cardiac dysfunction during sepsis, but the actual species responsible remains unclear. We studied the alterations in myocardial nitric oxide (NO), superoxide, and peroxynitrite generation along with cardiac mechanical function and efficiency in hearts from lipopolysaccharide (LPS)-treated rats. Six hours after LPS (4 mg/kg ip) or saline (control) treatment, hearts were isolated and perfused for 1 h with recirculating Krebs-Henseleit buffer and paced at 300 beats/min. Cardiac work, O2 consumption, and cardiac efficiency were markedly depressed in LPS hearts compared with controls. Plasma nitrate/nitrite level was elevated in LPS rats, and ventricular NO production was enhanced as measured by electron spin resonance spectroscopy, Ca2+-independent NO synthase (NOS) activity, and inducible NOS immunohistochemistry. Ventricular superoxide production was also enhanced in LPS-treated hearts as seen by lucigenin chemiluminescence and xanthine oxidase activity. Increased nitrotyrosine staining (immunohistochemistry) and higher lipid hydroperoxides levels were also detected in LPS-treated hearts, indicating oxygen radical-induced stress. Enhanced generation of both NO and superoxide, and thus peroxynitrite, occur in dysfunctional hearts from endotoxemic rats.",
keywords = "Cardiac dysfunction, Nitric oxide, Sepsis, Superoxide and peroxynitrite",
author = "Khadour, {Fadi H.} and Donna Panas and P. Ferdin{\'a}ndy and Costas Schulze and T. Csont and Lalu, {Manoj M.} and Wildhirt, {Stephen M.} and Richard Schulz",
year = "2002",
language = "English",
volume = "283",
journal = "American Journal of Physiology",
issn = "0363-6119",
publisher = "American Physiological Society",
number = "3 52-3",

}

TY - JOUR

T1 - Enhanced NO and superoxide generation in dysfunctional hearts from endotoxemic rats

AU - Khadour, Fadi H.

AU - Panas, Donna

AU - Ferdinándy, P.

AU - Schulze, Costas

AU - Csont, T.

AU - Lalu, Manoj M.

AU - Wildhirt, Stephen M.

AU - Schulz, Richard

PY - 2002

Y1 - 2002

N2 - Free radicals have been implicated in the etiology of cardiac dysfunction during sepsis, but the actual species responsible remains unclear. We studied the alterations in myocardial nitric oxide (NO), superoxide, and peroxynitrite generation along with cardiac mechanical function and efficiency in hearts from lipopolysaccharide (LPS)-treated rats. Six hours after LPS (4 mg/kg ip) or saline (control) treatment, hearts were isolated and perfused for 1 h with recirculating Krebs-Henseleit buffer and paced at 300 beats/min. Cardiac work, O2 consumption, and cardiac efficiency were markedly depressed in LPS hearts compared with controls. Plasma nitrate/nitrite level was elevated in LPS rats, and ventricular NO production was enhanced as measured by electron spin resonance spectroscopy, Ca2+-independent NO synthase (NOS) activity, and inducible NOS immunohistochemistry. Ventricular superoxide production was also enhanced in LPS-treated hearts as seen by lucigenin chemiluminescence and xanthine oxidase activity. Increased nitrotyrosine staining (immunohistochemistry) and higher lipid hydroperoxides levels were also detected in LPS-treated hearts, indicating oxygen radical-induced stress. Enhanced generation of both NO and superoxide, and thus peroxynitrite, occur in dysfunctional hearts from endotoxemic rats.

AB - Free radicals have been implicated in the etiology of cardiac dysfunction during sepsis, but the actual species responsible remains unclear. We studied the alterations in myocardial nitric oxide (NO), superoxide, and peroxynitrite generation along with cardiac mechanical function and efficiency in hearts from lipopolysaccharide (LPS)-treated rats. Six hours after LPS (4 mg/kg ip) or saline (control) treatment, hearts were isolated and perfused for 1 h with recirculating Krebs-Henseleit buffer and paced at 300 beats/min. Cardiac work, O2 consumption, and cardiac efficiency were markedly depressed in LPS hearts compared with controls. Plasma nitrate/nitrite level was elevated in LPS rats, and ventricular NO production was enhanced as measured by electron spin resonance spectroscopy, Ca2+-independent NO synthase (NOS) activity, and inducible NOS immunohistochemistry. Ventricular superoxide production was also enhanced in LPS-treated hearts as seen by lucigenin chemiluminescence and xanthine oxidase activity. Increased nitrotyrosine staining (immunohistochemistry) and higher lipid hydroperoxides levels were also detected in LPS-treated hearts, indicating oxygen radical-induced stress. Enhanced generation of both NO and superoxide, and thus peroxynitrite, occur in dysfunctional hearts from endotoxemic rats.

KW - Cardiac dysfunction

KW - Nitric oxide

KW - Sepsis

KW - Superoxide and peroxynitrite

UR - http://www.scopus.com/inward/record.url?scp=0036350478&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036350478&partnerID=8YFLogxK

M3 - Article

C2 - 12181141

AN - SCOPUS:0036350478

VL - 283

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6119

IS - 3 52-3

ER -