TY - JOUR
T1 - Inhibition of prostaglandins does not reduce the cardiovascular changes during endotoxemia in rats
AU - Azab, Abed
AU - Kobal, Sergio
AU - Rubin, Mazal
AU - Kaplanski, Jacob
PY - 2006/2/1
Y1 - 2006/2/1
N2 - 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-α and IL-1β 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 PGE 2 is not sufficient to reduce the cardiovascular alteration seen in endotoxemia.
AB - 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-α and IL-1β 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 PGE 2 is not sufficient to reduce the cardiovascular alteration seen in endotoxemia.
UR - http://www.scopus.com/inward/record.url?scp=30544436874&partnerID=8YFLogxK
U2 - 10.1016/j.plefa.2005.10.004
DO - 10.1016/j.plefa.2005.10.004
M3 - Article
C2 - 16343878
AN - SCOPUS:30544436874
SN - 0952-3278
VL - 74
SP - 135
EP - 142
JO - Prostaglandins Leukotrienes and Essential Fatty Acids
JF - Prostaglandins Leukotrienes and Essential Fatty Acids
IS - 2
ER -
