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Cardiac response to nitric oxide synthase inhibition using aminoguanidine in a rat model of endotoxemia.

Authors
Vona-Davis-L; Wearden-P; Millecchia-L; Hill-J; Timberlake-G; Hill-R
Source
Shock 1999 Jun; 11(Suppl 1):51
NIOSHTIC No.
20030732
Abstract
This study evaluates the effect of aminoguanidine, a preferential inhibitor of inducible nitric oxide synthase (iNOS) on the prevention of cardiac depression in acute endotoxemia. Cardiac performance was evaluated after 4 hr of exposure to endotoxin. Animals were randomly selected to receive by i.p. injection one of 4 treatments (n=5 per treatment); Saline, LPS (lipopolysaccharide, E. Coli. 4mg/kg), AG (amino guanidine 100 mg/kg) and LPS plus AG at various times. AG and saline treatments were administered 30 min before LPS and at I and 3 hr after LPS injection. Hearts were perfused using the Langendorff preparation and a balloon tipped catheter was placed in the left ventricle to measure left ventricular developed pressure (L VDP). Myocyte contractile function was assessed with electrical field stimulation and video microscopy. Tissue was immunostained for the expression of iNOS and for nitrotyrosine, a byproduct of protein nitration by peroxynitrite. Perfused hearts from LPS-treated rats exhibited a 57% decrease (P=.0001) in L VDP compared to saline-treated animals. No improvement in ventricular function was observed with the administration of AG. Similarly, cardiac myocytes prepared from LPS-treated animals demonstrated a significant (P<.05) reduction in percent and velocity of shortening and this effect was unaltered with the same dose of AG. Aminoguanidine administration significantly (P=.0003) reduced serum nitrite/nitrate levels in endotoxemic rats to control levels. Localized expression of iNOS in the myocardium was lessened with AG treatment and was not associated with peroxynitrite formation in this model of endotoxemia. The results indicate that AG given i.p. before and after endotoxin (at a concentration sufficient to decrease: nitric oxide production) did not reduce cardiac depression. We conclude that selective inhibition of iNOS and reduction of nitric oxide production do not prevent cardiac dysfunction in an acute model of endotoxic shock.
Keywords
Animal-studies; Animals; Laboratory-animals; Cardiac-function; Cardiovascular-function; Cardiovascular-system; Cardiovascular-system-disorders; Exposure-assessment; Endotoxins; Toxic-effects; Toxic-materials; Toxins
CODEN
SAGUAI
CAS No.
10102-43-9
Publication Date
19990601
Document Type
Conference/Symposia Proceedings; Abstract
Fiscal Year
1999
NTIS Accession No.
NTIS Price
ISSN
1073-2322
NIOSH Division
HELD
Source Name
Shock. Abstracts of the fourth International Shock Conbress and Twenty-Second annual Conference on Shock
State
WV
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