Inhibition of prostaglandins does not reduce the cardiovascular changes during endotoxemia in rats

Vasodilatory prostanoids, such as prostacyclin and PGE(2), and pro-inflammatory cytokines are known to play a central role in the pathogenesis of endotoxemia. This study was undertaken to elucidate whether indomethacin (INDO), a non-selective COX inhibitor, has protective effects against the cardiovascular alterations that occur during endotoxemia. Sprague-Dawley rats were injected intraperitoneally with 15mg/kg lipopolysaccharide (LPS). LPS injection led to a prominent decrease in cardiac left ventricular end diastolic area (LVEDA) and increased LV fractional shortening (FS), as measured by echocardigraphy. LPS also led to a significant increase in plasma and myocardial TNF-alpha and IL-1 beta levels, and elevated plasma and hypothalamic levels of PGE(2). Neither the decrease in LVEDA and the increase in FS, nor the elevation in plasma and myocardial cytokine levels were altered by INDO (10 mg/kg). On the other hand, pretreatment with INDO significantly reduced the elevation in PGE(2) and the hypothermia induced by LPS. Taken together, this study demonstrates that solely inhibiting the production of PGE(2) is not sufficient to reduce the cardiovascular alteration seen in endotoxemia. (c) 2005 Elsevier Ltd. All rights reserved.