Prasannajit Dutta, Deanne E. Ryan and Reza Tabrizchi*
Division of Basic Medical Sciences, Faculty of Medicine, Memorial University
of Newfoundland, St. John's, NF, Canada
*Corresponding author. FAX: +1-709-737-7010
E-mail: rtabrizc@morgan.ucs.mun.ca
Abstract: Administration of bacterial endotoxin (lipopolysaccharide,
LPS) intravenously has been noted to produce a shock state, which is characterized
by hypotension and mutli-organ system failure. The aim of the present investigation
was to (a) examine the influence of rolipram on hemodynamics, plasma levels
of tumor necrosis factor-a (TNF-a)
levels, and production of inducible nitric oxide synthase (iNOS) in the
lungs, ex vivo, in LPS-treated rats, and (b) determine the cardiovascular
effects of a selective a1-adrenoceptor
agonist, methoxamine, in the absence or presence of rolipram in rats treated
with LPS. Blood pressure, cardiac index, heart rate and arterial resistance
were assessed in Long-Evans rats anesthetized with thiobutabarbital. Administration
of LPS to animals resulted in a significant reduction in cardiac index over
time. The administration of LPS to rats resulted in a substantial rise in
the plasma levels of TNF-a. Furthermore, the injection
of LPS resulted in a significant increase in the iNOS activity in the lungs.
Pre-treatment with rolipram prevented the decline in cardiac index in animals
that received LPS. Infusion of methoxamine into animals injected with rolipram
and pre-treated with LPS did not result in significant changes in cardiac
index. Pre-treatment with rolipram or dexamethasone in animals injected
with LPS significantly prevented the rise in TNF-a
when compared to the respective values in vehicle-treated animals. Our present
observations support the view that the cardiac index can be maintained in
animals treated with LPS independent of iNOS inhibition.
Keywords: Lipopolysacharride, Hemodynamics, Tumor necrosis factor-a,
Nitric oxide synthase, a1-Adrenoceptor
stimulation
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