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(Hypertension. 2002;40:947.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Cyclooxygenase-2 Inhibition Attenuates Lipopolysaccharide-Induced Cardiovascular Failure

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

Correspondence to Michael Bucher, MD, Department of Anesthesiology, University of Regensburg, 93042 Regensburg, Germany. E-mail michael.bucher{at}klinik.uni-regensburg.de

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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