Inhibition of prostaglandins does not reduce the cardiovascular changes during endotoxemia in rats.
Vasodilatory prostanoids, such as prostacyclin and PGE2, 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 15 mg/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-1beta levels, and elevated plasma and hypothalamic levels of PGE2. 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 PGE2 and the hypothermia induced by LPS. Taken together, this study demonstrates that solely inhibiting the production of PGE2 is not sufficient to reduce the cardiovascular alteration seen in endotoxemia.
Azab
Abed
A
Department of Clinical Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, PO Box 154 Beer-Sheva 84105, Israel.
Kobal
Sergio
S
Rubin
Mazal
M
Kaplanski
Jacob
J
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood; D019446:Endotoxemia / Q000139:chemically induced / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects*; D007031:Hypothalamus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D007035:Hypothermia / Q000139:chemically induced / Q000188:drug therapy; D007213:Indomethacin / Q000494:pharmacology*; D007375:Interleukin-1 / Q000097:blood / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone; D007213:Indomethacin; D004121:Dimethyl Sulfoxide