Inhibitory effect of SM-20550, an Na+/H+ exchange inhibitor, on accumulation of leukocytes in ischemia and reperfusion.
The effect of an Na+/H+ exchange inhibitor, SM-20550, on the adhesion, emigration and accumulation of leukocytes was studied in ischemia and reperfusion injury models using rat mesenteric venules or rabbit heart. Anesthetized rats underwent occlusion of the superior mesenteric artery (20 min) followed by reperfusion (60 min). After ischemia and reperfusion, the numbers of adherent and emigrated leukocytes increased significantly. Bolus intravenous administration of SM-20550 reduced the numbers of adherent and emigrated leukocytes in a dose-dependent manner, with statistical significance at dosages >0.1 mg/kg. Anesthetized rabbits underwent occlusion of the coronary artery (30 min) followed by reperfusion (5 h). Intravenous administration of SM-20550 before ischemia significantly reduced the neutrophil accumulation in the area-at-risk by 46% and reduced the infarct size by 38%. These results suggest that the inhibitory effect of SM-20550 on the neutrophil accumulation could be one of the mechanisms by which this drug limits the severity of infarctions.
Yamada
K
K
Sumitomo Pharmaceuticals Co, Ltd, Research Center, Osaka, Japan. yamadak@sumitomopharm.co.jp
Horikawa
N
N
Matsui
K
K
Yamamoto
S
S
Kawamura
N
N
Ohashi
N
N
D000578:Amidines / Q000627:therapeutic use*; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D007211:Indoles / Q000627:therapeutic use*; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009203:Myocardial Infarction / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010750:Phosphoproteins / Q000037:antagonists & inhibitors; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D017923:Sodium-Hydrogen Exchangers
D000578:Amidines; D007211:Indoles; D010750:Phosphoproteins; C121094:SM 20550; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor