Published Online
on October 28, 2002

A more recent version of this article appeared on December 1, 2002

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Submitted on August 8, 2002
Revised on September 12, 2002

Cyclooxygenase-2 Inhibition Attenuates Lipopolysaccharide-Induced Cardiovascular Failure

Klaus Höcherl; Franziska Dreher; Armin Kurtz; and Michael Bucher^*

From the Departments of Pharmacology (K.H., F.D.), Physiology (A.K.), and Anesthesiology (M.B.), University of Regensburg, Regensburg, Germany.

^* To whom correspondence should be addressed. E-mail: michael.bucher{at}klinik.uni-regensburg.de.

Abstract—The present study aimed to determine the relevance of cyclooxygenase-2 (COX-2)-derived prostanoids for the adverse effects of lipopolysaccharides (LPSs) on cardiovascular function. For this goal, male Sprague-Dawley rats received a single intravenous dose of LPS (10 mg/kg) and were treated with different cyclooxygenase inhibitors. Injection of LPS caused a marked decrease of systolic arterial pressure, from 128 to 79 mm Hg, and a concomitant increase of heart rate, from 380 to 530 minutes^-1. Both the decrease of systemic arterial pressure and the increase of heart rate induced by LPS were almost absent if the animals also received the COX-2 blocker rofecoxib (20 mg/kg), regardless whether the drug was given 1 hour before or 1 hour after LPS. Although plasma and organ levels of prostanoids were lowered by rofecoxib, the characteristic LPS-induced increases of NO synthase II and COX-2 gene expression, as well as of plasma and tissue nitrate/nitrite concentrations, were not affected by rofecoxib. Although rofecoxib treatment did also not change LPS-induced tissue cytokine concentrations, it markedly improved LPS-induced liver damage, as indicated by the decrease of transaminases. Moreover, the overall well-being of the LPS-injected animals improved on concomitant treatment with the COX-2 inhibitor. Taken together, our data suggest that COX-2-derived prostanoids are major mediators for the detrimental effects of LPS on cardiovascular and organ function.

Key words: shock • cyclooxygenase • hemodynamics • prostaglandins • nitric oxide

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