Ischemia-reperfusion lung injury attenuated by ATP-MgCl2 in rats.
The protective effect of ATP-MgCl2 on ischemia-reperfusion lung injury has been reported in kidney, liver, heart, and muscle but has not been examined in lungs. The aim of this study was to determine whether ATP or ATP-MgCl2 pretreatment would attenuate ischemia-reperfusion-induced acute lung injury and to identify the possible mechanisms for such protection. Typical acute lung injury was successfully induced in Sprague-Dawley rats by 10 min of hypoxia followed by 75 min of ischemia and 50 min of reperfusion. Pretreatment with ATP-MgCl2 (or adenosine) but not ATP or MgCl2 (all at 10(-6) M) significantly attenuated the acute lung injury. All the protective effects of ATP-MgCl2 were nearly undetectable when promazine (an ecto-adenosinetriphosphatase inhibitor) or 3,7-dimethyl-1-propargylxanthine (an A2-receptor antagonist) was added before ATP-MgCl2 pretreatment. These observations support our hypothesis that the protective effect of ATP-MgCl2 is in part mediated through adenosine, the degradation product of ATP, which is produced by the Mg(2+)-dependent ecto-adenosinetriphosphatase on the surface of neutrophils and reacts with neutrophil A2 receptors to inhibit the production of O2 radicals.
Hsu
K
K
Department of Medicine, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
Wang
D
D
Wu
S Y
SY
Shen
C Y
CY
Chen
H I
HI
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D004338:Drug Combinations; D007962:Leukocytes / Q000502:physiology; D008163:Luminescent Measurements; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D015636:Magnesium Chloride / Q000494:pharmacology*; D008297:Male; D009929:Organ Size; D011506:Proteins / Q000378:metabolism; D011651:Pulmonary Artery / Q000503:physiopathology; D011652:Pulmonary Circulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D014655:Vascular Resistance
D004338:Drug Combinations; D011506:Proteins; D015636:Magnesium Chloride; D000255:Adenosine Triphosphate