Effects of inhibition of nitric oxide synthase (nos) by
aminoguanidine in acute endotoxemia.
Hock, Carl E., Kingsley Yin, Gang Yue, and Patrick Y-K Wong.
Departments of Medicine and Cell Biology, University of Medicine
and Dentistry of New Jersey, School of Osteopathic Medicine,
Stratford, NJ 08084
APStracts 3:0353H, 1996.
Nitric oxide (NO) has been implicated in the pathogenesis of the
circulatory dysfunction of endotoxin shock. We investigated the
effect of aminoguanidine (AG), an inhibitor of nitric oxide synthase
(NOS) that is more selective for the inducible NOS (iNOS), on the
circulatory and inflammatory sequelae following administration of a
bolus (10 mg/kg, i.v.) of lipopolysaccharide (LPS) (salmonella
enteritidis). Rats receiving LPS+Vehicle (LPS+VEH) exhibited a 73%
decrease in mean arterial blood pressure (MABP) and a 50% decrease in
cardiac index (CI) and SV index (SVI) within 10 min following LPS
administration. MABP recovered to 64+/-3, 81+/-6 and 79+/-8 mmHg, at
60, 120 and 180 min post LPS, respectively. However, CI and SVI
remained depressed by 40-50% for the entire experimental period.
Systemic vascular resistance (SVRI), HR and hematocrit were
significantly elevated at 180 min following LPS administration. There
was a 15-fold increase in plasma nitrite/nitrate and significantly
elevated tissue nitrite/nitrate in the lung, heart, liver and
intestine after 3 hours of acute endotoxemia. Treatment with AG
markedly decreased plasma nitrite/nitrate but did not alter the
initial hypotension or cardiac depression. However, at 60 min
following LPS administration the HR, MABP and SVRI were higher in the
AG-treated rats compared to vehicle, while, CI and SVI remained
depressed. Myeloperoxidase (MPO) activity was significantly increased
in the lung but not in the other tissues following LPS. The AG
infusion significantly reduced tissue nitrite/nitrate in the lung and
heart when compared to LPS+VEH. The data suggest that neither NO nor
acute inflammatory cell accumulation is solely responsible for the
depressed cardiovascular function following i.v., administration of
LPS.
Received 3 November 1995; accepted in final form 8 August 1994.
APS Manuscript Number H1031-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996