| Autor: |
Horikawa, Naotsugu, Kuribayashi, Yoshikazu, Matsui, Kazuki, Kawamura, Nobuko, Ohashi, Naohito |
| Zdroj: |
Journal of Cardiovascular Pharmacology; June 2001, Vol. 37 Issue: 6 p668-677, 10p |
| Abstrakt: |
Leukocytes play a key role in ischemiareperfusioninduced tissue injuries. It has been suggested that blocking the NaHexchanger improves ischemic injuries such as stroke. In this study, we investigated the effect of the NaHexchanger inhibitor SM20220 Naminoiminomethyl1methyl1Hindole2carboxamide methanesulfonate on leukocyteendothelial cell interactions during ischemiareperfusion. SM20220 0.3–1.0 mgkg i.v. given after ischemia significantly attenuated the leukocyte adhesion in the mesenteric postcapillary venules that was induced by transient superior mesenteric artery occlusion. At 60 min after reperfusion, the numbers of adherent leukocytes in groups treated with vehicle or SM20220 0.3 mgkg were 15.1 ± 2.9 cells100 m3 min and 3.0 ± 0.7 cells100 m3 min p < 0.01, respectively. In a transient middle cerebral artery occlusion model, i.v. infusion of SM20220 0.4 mgkg per hour for 1 h, beginning 1 h after the start of occlusion, significantly reduced both the infarct size and the increase in brain myeloperoxidase activity, compared with the vehicle group p < 0.01 and p < 0.05, respectively. In summary, this is the first evidence that the leukocyte adhesion to the endothelium that is induced by ischemiareperfusion is attenuated by the inhibition of NaHexchanger activity in vivo. Our results suggest that NaHexchanger inhibitors may prevent ischemiareperfusion injuries such as stroke partly through the attenuation of leukocyteendothelial cell interactions. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
