Biomedical Research
Online ISSN : 1880-313X
Print ISSN : 0388-6107
ISSN-L : 0388-6107
Full Papers
Time-dependent expression of endothelin-1 in lungs and the effects of TNF-α blocking peptide on acute lung injury in an endotoxemic rat model
Subrina JesminNaoto YamaguchiSohel ZaediSayeeda Nusrat SultanaYoshio IwashimaAtsushi SawamuraSatoshi Gando
ジャーナル フリー

2011 年 32 巻 1 号 p. 9-17


Endothelin (ET)-1 is a potent vasoconstrictor that has been implicated in the pathogenesis of a number of diseases, and some studies suggest that circulating ET-1 is elevated in sepsis. The present study investigated whether ET plays a role in sepsis-mediated acute lung injury and whether its expression could be down regulated by blockade of TNF-α in septic lung. Male Wistar rats at 8 weeks of age were administered with either saline or lipopolysaccharide (LPS) at different time points (1, 3, 6 and 10 h) and various tests were then performed. The features of acute lung injury were observed at 1 h after LPS administration, which gradually became severe with time. Systolic and diastolic pressures were reduced just about one hour after LPS administration, whereas pulmonary TNF-α levels were significantly increased at various time points after LPS administration. LPS induced a time-dependent expression of ET-1 and ETA receptor in the lungs compared to control, peaking and incre sing by 3 fold at 6 h after induction of endotoxemia, whereas levels of ETB receptor, which has vasodilating effects, were remarkably down regulated time-dependently. We conclude that time-dependent increase of ET-1 and ETA receptor with the down regulation of ETB receptor may play a role in the pathogenesis of acute lung injury in endotoxemia. Finally, treatment of LPS-administered rats with TNF-α blocking peptide for three hours significantly suppressed levels of pulmonary ET-1. These data taken together, led us to conclude that differential alteration in ET expression and its receptors may be mediated by TNF-α and may, in part, account for the pathogenesis of acute lung injury in endotoxemia.

© 2011 Biomedical Research Press
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