Role of poly(ADP-ribose) polymerase activation in endotoxin-induced cardiac collapse in rodents

P. Pacher, A. Cziraki, Jon Mabley, L. Liaudet, L Papp, C. Szabo

Research output: Contribution to journalArticle

Abstract

Reactive oxygen and nitrogen species are overproduced in the cardiovascular system during circulatory shock. Oxidant-induced cell injury involves the activation of poly(ADP-ribose) polymerase (PARP). Using a dual approach of PARP-1 suppression, by genetic deletion or pharmacological inhibition with the new potent phenanthridinone PARP inhibitor PJ34 [the hydrochloride salt of N-(oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide], we studied whether the impaired cardiac function in endotoxic shock is dependent upon the PARP pathway. Escherichia coli endotoxin (lipopolysaccharide, LPS) at 55 mg/kg, i.p., induced a severe depression of the systolic and diastolic contractile function, tachycardia, and a reduction in mean arterial blood pressure in both rats and mice. Treatment with PJ34 significantly improved cardiac function and increased the survival of rodents. In addition, LPS-induced depression of left ventricular performance was significantly less pronounced in PARP-1 knockout mice (PARP−/−) as compared with their wild-type littermates (PARP+/+). Thus, PARP activation in the cardiovascular system is an important contributory factor to the cardiac collapse and death associated with endotoxin shock.
Original languageEnglish
Pages (from-to)1785-1791
Number of pages7
JournalBiochemical Pharmacology
Volume64
Issue number12
DOIs
Publication statusPublished - Dec 2002

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Poly(ADP-ribose) Polymerases
Endotoxins
Rodentia
Cardiovascular System
Lipopolysaccharides
Shock
Arterial Pressure
Genetic Suppression
Reactive Nitrogen Species
Septic Shock
Oxidants
Tachycardia
Knockout Mice
Reactive Oxygen Species
Salts
Pharmacology
Wounds and Injuries

Keywords

  • Poly(ADP-ribose) polymerase
  • Endotoxin
  • Shock
  • Cardiac collapse
  • Cardiac function

Cite this

Pacher, P. ; Cziraki, A. ; Mabley, Jon ; Liaudet, L. ; Papp, L ; Szabo, C. / Role of poly(ADP-ribose) polymerase activation in endotoxin-induced cardiac collapse in rodents. In: Biochemical Pharmacology. 2002 ; Vol. 64, No. 12. pp. 1785-1791.
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Role of poly(ADP-ribose) polymerase activation in endotoxin-induced cardiac collapse in rodents. / Pacher, P.; Cziraki, A.; Mabley, Jon; Liaudet, L.; Papp, L; Szabo, C.

In: Biochemical Pharmacology, Vol. 64, No. 12, 12.2002, p. 1785-1791.

Research output: Contribution to journalArticle

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AU - Cziraki, A.

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AU - Szabo, C.

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