Effects of pulmonary oedema on pharmacokinetics of adenosine in rat isolated lungs

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Abstract
1 Pulmonary oedema, assessed by decreases in the lung dry weight:wet weight ratio, was induced in rats by a single i.p. injection of α-naphthylthiourea (ANTU). The oedema reached a peak at 4 h after ANTU and had completely resolved after 28 h. 2 Pulmonary pharmacokinetics of adenosine were measured in isolated, perfused lungs using radiolabelled adenosine and sucrose, injected into the perfusate as a single bolus. 3 By 1 h after ANTU the 1 min efflux of tracer for adenosine increased to over 60% and remained high until 16 h after ANTU. The time for 50% of injected radioactivity to appear in lung effluent (t1/2) for adenosine was reduced from its normal value of > 120 s to a minimum of 27 s at 1 h after ANTU. The proportion of adenosine in lung effluent did not change until 16 h after ANTU treatment but returned to normal by 50 h. 4 There were only minimal changes in the T1/2 and 1 min efflux for sucrose following ANTU treatment. 5 It appears that both the uptake and metabolism of adenosine are affected by ANTU-induced lung damage. The early effects are chiefly on uptake with metabolism remaining normal. Later (after 16 h) metabolism is decreased with uptake recovering to normal levels. 6 The effects on adenosine uptake paralleled the development and the resolution of oedema, suggesting that this variable might provide a biochemical index of the physical processes leading to lung oedema.