返回Google圖書搜尋

Endothelin-endothelial Nitric Oxide Synthase Interaction in Experimental Endotoxemia

出版	University of North Carolina at Charlotte, 2004
URL	http://books.google.com.hk/books?id=GIt3nQEACAAJ&hl=&source=gbs_api

註釋Dysfunctional microcirculation is one of the hallmarks of hepatic failure. An enhanced constrictor response in the liver to endothelin-1 is observed in conditions that lead to hepatic failure. Hyperconstriction in response to endothelin-1 occurs in spite of its ability to stimulate eNOS in sinusoidal endothelial cells in the normal liver and in spite of an increase in endothelin B receptor expression following stress. An uncoupling of endothelin B receptor activation and stimulation of eNOS activity may contribute to the hyperconstrictive effects of endothelin-1. The likely site of endothelin-B receptor-mediated eNOS activity is the sinusoidal endothelial cell. Here, eNOS is regulated by protein interactions with caveolin-1 and calmodulin, and by intracellular localization. In this study, we first developed a model for investigating endothelin-1 regulation of eNOS activity in sinusoidal endothelial cells. Second, we determined the effect of endothelin-1 on caveolin-1 expression, eNOS localization, and eNOS/caveolin-1 co-localization in sinusoidal endothelial cells. Thirdly, we determined whether LPS alters caveolin-1 expression, eNOS localization, eNOS/caveolin-1 co-localization, and endothelin-1-induced eNOS activity in sinusoidal endothelial cells. Taken together, the results of these studies will provide insight into the role of altered eNOS regulation in sinusoidal endothelial cells in the hyperconstrictive response of the liver to endothelin-1 during inflammatory conditions.