ADENOSINE PREVENTS PMA-INDUCED LUNG INJURY VIA AN A2-RECEPTOR MECHANISM

被引:25
作者
ADKINS, WK [1 ]
BARNARD, JW [1 ]
MOORE, TM [1 ]
ALLISON, RC [1 ]
PRASAD, VR [1 ]
TAYLOR, AE [1 ]
机构
[1] UNIV SO ALABAMA,COLL MED,DEPT PHYSIOL,MSB 3024,MOBILE,AL 36688
关键词
CAPILLARY FILTRATION COEFFICIENT; LUNG INJURY; ISOLATED LUNGS; NEUTROPHILS;
D O I
10.1152/jappl.1993.74.3.982
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Previous studies indicate that adenosine attenuates phorbol myristate acetate- (PMA) induced canine lung injury, but the mechanism has not been explained. To evaluate adenosine's protective mechanism, isolated and blood-perfused dog lungs were challenged by PMA (50 mug) under control conditions and after both pre- and posttreatment with adenosine and pretreatment with 2-chloro-N6-cyclopentyladenosine (CCPA), 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamido adenosine (CGS 21680C), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; PD-116948), or isoproterenol. Injury was assessed by measurement of the capillary filtration coefficient (K(f,c)), and pulmonary vascular resistance was measured. PMA increased the K(f,c) (0.170 +/- 0.015 to 1.030 +/- 0.167 ml . min-1 . cmH2O-1 . 100 g lung wet wt-1) and the total pulmonary vascular resistance (18.2 +/- 3.8 to 110.2 +/-60.8 cmH2O . l-1 . min . 100 g lung wet wt). Pretreatment with adenosine, A2 agonist, A1 antagonist, and isoproterenol blocked the increase in K(f,c) induced by PMA. These agents also slightly attenuated the resistance increase induced by PMA, with the exception of the A1 antagonist, which completely prevented the resistance increase (24.3 +/- 7.8 to 23.4 +/- 8.1 cmH2O. l-1 . min . 100 g lung wet wt). The A1 agonist also slightly attenuated the increase in K(f,c) (0.174 +/- 0.022 to 0.486 +/- 0.128 ml . min-1 . cmH2O-1 . 100 g lung wet wt-1) and did not affect the resistance increase. Posttreatment with adenosine did not significantly affect the changes induced by PMA. These data show that PMA-induced increases in capillary permeability in the isolated blood-perfused dog lung can be blocked by pretreatment with adenosine, which binds the adenosine A2 receptors.
引用
收藏
页码:982 / 988
页数:7
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