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Table of Contents
Vol. 103, No. 2, 2005
Issue release date: February 2005
Cardiology 2005;103:92–100
(DOI:10.1159/000082470)

Effects of Nimesulide, a Selective Cyclooxygenase-2 Inhibitor, on Cardiovascular Alterations in Endotoxemia

Azab A.N. · Kobal S. · Rubin M. · Kaplanski J.
aDepartment of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, and bDepartment of Cardiology, Soroka University Medical Center, Beer-Sheva, Israel

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Abstract

Prostanoids and cytokines are known to play a pivotal role in the mechanisms leading to endotoxin-induced cardiovascular failure. We investigated the effect of nimesulide (NIM), a selective cyclooxygenase-2 (COX-2) inhibitor, on the cardiovascular alterations occurring during endotoxemia, and on prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels in endotoxemic rats. NIM significantly reduced endotoxin-induced elevation of plasma and myocardial levels of TNF-α, but not those of IL-1β. Searching for the mechanism underlying the anti-TNF-α effect of NIM, it was found that the drug reduced nuclear factor kappa B activation through diminished nuclear levels of p-65 accompanied by a protective effect against the cardiovascular alterations and mortality seen during endotoxemia. In addition, the inhibitory effect of NIM on endotoxin-induced elevation in plasma and hypothalamic levels of PGE2 was noteworthy, and this may suggest that the large amounts of PGE2 observed during endotoxemia are mainly produced via COX-2.



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