Role of bacteria and inducible nitric oxide synthase activity in the systemic inflammatory microvascular response provoked by indomethacin in the rat

2003 ◽  
Vol 461 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Steven M Evans ◽  
Brendan J.R Whittle
Circulation ◽  
1997 ◽  
Vol 96 (9) ◽  
pp. 3104-3111 ◽  
Author(s):  
Yoshihiro Fukumoto ◽  
Hiroaki Shimokawa ◽  
Toshiyuki Kozai ◽  
Toshiaki Kadokami ◽  
Kouichi Kuwata ◽  
...  

Nitric Oxide ◽  
2001 ◽  
Vol 5 (2) ◽  
pp. 208-211 ◽  
Author(s):  
Jean-Charles Preiser ◽  
Haibo Zhang ◽  
Bernard Vray ◽  
Andreas Hrabak ◽  
Jean-Louis Vincent

2007 ◽  
Vol 103 (3) ◽  
pp. 1045-1055 ◽  
Author(s):  
Juliann G. Kiang ◽  
Phillip D. Bowman ◽  
Xinyue Lu ◽  
Yansong Li ◽  
Brian W. Wu ◽  
...  

Hemorrhage has been shown to increase inducible nitric oxide synthase (iNOS) and deplete ATP levels in tissues and geldanamycin limits both processes. Moreover, it is evident that inhibition of iNOS reduces caspase-3 and increases survival. Thus we sought to identify the molecular events responsible for the beneficial effect of geldanamycin. Hemorrhage in mice significantly increased caspase-3 activity and protein while treatment with geldanamycin significantly limited these increases. Similarly, geldanamycin inhibited increases in proteins forming the apoptosome (a complex of caspase-9, cytochrome c, and Apaf-1). Modulation of the expression of iNOS by iNOS gene transfection or siRNA treatment demonstrated that the level of iNOS correlates with caspase-3 activity. Our data indicate that geldanamycin limits caspase-3 expression and protects from organ injury by suppressing iNOS expression and apoptosome formation. Geldanamycin, therefore, may prove useful as an adjuvant in fluids used to treat patients suffering blood loss.


Sign in / Sign up

Export Citation Format

Share Document