A synthetic analogue of 20-HETE, 5,14-HEDGE, reverses endotoxin-induced hypotension via increased 20-HETE levels associated with decreased iNOS protein expression and vasodilator prostanoid production in rats.
A synthetic analogue of 20-HETE, 5,14-HEDGE, reverses endotoxin-induced hypotension via increased 20-HETE levels associated with decreased iNOS protein expression and vasodilator prostanoid production in rats.
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DOI：
10.1111/j.1742-7843.2009.00501.x
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发表时间：
2010-05
影响因子：
3.1
通讯作者：
Tunctan B
中科院分区：
文献类型：
--
作者：
Cuez T;Korkmaz B;Buharalioglu CK;Sahan-Firat S;Falck J;Malik KU;Tunctan B
Nitric oxide (NO) produced by inducible NO synthase (iNOS) is responsible for endotoxin-induced hypotension and vascular hyporeactivity and plays a major contributory role in the multiorgan failure. Endotoxic shock is also associated with an increase in vasodilator prostanoids as well as a decrease in endothelial NO synthase (eNOS) and cytochrome P450 4A protein expression, and production of a vasoconstrictor arachidonic acid product, 20-hydroxyeicosatetraenoic acid (20-HETE). The aim of this study was to investigate the effects of a synthetic analogue of 20-HETE, N-[20-hydroxyeicosa-5(Z),14(Z)-dienoyl]glycine (5,14-HEDGE), on the endotoxin-induced changes in eNOS, iNOS and heat shock protein 90 (hsp90) expression as well as 20-HETE and vasodilator prostanoid (6-keto-PGF1α and PGE2) production. Endotoxin-induced fall in blood pressure and rise in heart rate were associated with an increase in iNOS protein expression and a decrease in eNOS protein expression in heart, thoracic aorta, kidney and superior mesenteric artery. Endotoxin did not change hsp90 protein expression in the tissues. Endotoxin-induced changes in eNOS and iNOS protein expression were associated with increased 6-keto-PGF1α and PGE2 levels and a decrease in 20-HETE levels, in the serum and kidney. These effects of endotoxin on the iNOS protein expression and 6-keto-PGF1α, PGE2 and 20-HETE levels were prevented by 5,14-HEDGE. Furthermore, a competitive antagonist of vasoconstrictor effects of 20-HETE, 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid, prevented the effects of 5,14-HEDGE on the endotoxin-induced changes in systemic and renal levels of these prostanoids and 20-HETE. These data are consistent with the view that an increase in systemic and renal 20-HETE levels associated with a decrease in iNOS protein expression and vasodilator prostanoid production contributes to the effect of 5,14-HEDGE to prevent the hypotension during rat endotoxemia.
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DOI：
10.1152/ajprenal.1998.275.3.f370
发表时间：
1998-09-01
影响因子：
4.2
作者：
Alonso-Galicia, M;Sun, CW;Roman, RJ
通讯作者：
Roman, RJ
影响因子：
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作者：
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DOI：
10.1152/ajprenal.1999.277.5.f790
发表时间：
1999-11-01
影响因子：
4.2
作者：
Alonso-Galicia, M;Falck, JR;Roman, RJ
通讯作者：
Roman, RJ
影响因子：
8.3
作者：
AlonsoGalicia, M;Drummond, HA;Roman, RJ
通讯作者：
Roman, RJ
影响因子：
3.1
作者：
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通讯作者：
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