|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 March 2002, Vol. 99, No. 5, pp. 1638-1645
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Antithrombin prevents endotoxin-induced hypotension by inhibiting
the induction of nitric oxide synthase in rats
Hirotaka Isobe,
Kenji Okajima,
Mitsuhiro Uchiba,
Naoaki Harada, and
Hiroaki Okabe
From the Department of Laboratory Medicine, Kumamoto
University School of Medicine, Japan.
Antithrombin (AT) prevents Escherichia coli-induced
hypotension in animal models of sepsis, and it further reduces the
mortality of patients with septic shock. In the present study, we
examined whether AT may prevent the endotoxin (ET)-induced hypotension by promoting the endothelial release of prostacyclin (PGI2)
in rats. Intravenous administration of AT (250 U/kg) prevented both hypotension and the increases in plasma levels of
NO2 /NO3 in rats
given ET. Lung expression of messenger RNA (mRNA) for tumor necrosis
factor- (TNF-) was transiently increased after ET administration,
followed by the increases in lung tissue levels of TNF-. Both the
lung activity of the inducible form of nitric oxide synthase (iNOS) and
the lung expression of iNOS mRNA in animals administered ET were
gradually increased after the TNF- mRNA expression had peaked.
Administration of AT significantly inhibited these increases. Neither
DEGR-F.Xa, a selective inhibitor of thrombin generation, nor
Trp49-modified AT, which is not capable of promoting the
endothelial release of PGI2, showed any effects on these
changes induced by ET. Administration of antirat TNF- antibody
produced effects similar to those induced by AT. Indomethacin
pretreatment abrogated the effects induced by AT. Iloprost, a stable
derivative of PGI2, produced effects similar to those of
AT. These findings suggested that AT prevents the ET-induced
hypotension by inhibiting the induction of iNOS through inhibiting
TNF- production. These effects of AT could be mediated by the
promotion of endothelial release of PGI2 and might at least
partly explain the therapeutic effects for septic shock.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
H. Tsuboi, Y. Naito, K. Katada, T. Takagi, O. Handa, S. Kokura, H. Ichikawa, N. Yoshida, M. Tsukada, and T. Yoshikawa
Role of the thrombin/protease-activated receptor 1 pathway in intestinal ischemia-reperfusion injury in rats
Am J Physiol Gastrointest Liver Physiol,
February 1, 2007;
292(2):
G678 - G683.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Saito, Y. Minamiya, U. Kalina, S. Saito, and J.-i. Ogawa
Effect of antithrombin III on neutrophil deformability
J. Leukoc. Biol.,
September 1, 2005;
78(3):
777 - 784.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Molor-Erdene, K. Okajima, H. Isobe, M. Uchiba, N. Harada, and H. Okabe
Urinary trypsin inhibitor reduces LPS-induced hypotension by suppressing tumor necrosis factor-{alpha} production through inhibition of Egr-1 expression
Am J Physiol Heart Circ Physiol,
March 1, 2005;
288(3):
H1265 - H1271.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. W. Kang, S. Y. Choi, M. K. Cho, C. H. Lee, and S. G. Kim
Thrombin Induces Nitric-oxide Synthase via Galpha 12/13-coupled Protein Kinase C-dependent I-kappa Balpha Phosphorylation and JNK-mediated I-kappa Balpha Degradation
J. Biol. Chem.,
May 2, 2003;
278(19):
17368 - 17378.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Mizutani, K. Okajima, M. Uchiba, H. Isobe, N. Harada, S. Mizutani, and T. Noguchi
Antithrombin reduces ischemia/reperfusion-induced renal injury in rats by inhibiting leukocyte activation through promotion of prostacyclin production
Blood,
April 15, 2003;
101(8):
3029 - 3036.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
