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

• Published in: British journal of pharmacology 1987-08, Vol.91 (4), p.849-856
• Main Authors: Bakhle, Y.S., Grantham, C.J.
• Format: Article
• Language: English
• Subjects: Adenosine - pharmacokinetics; Animals; Applied sciences; Chromatography, Thin Layer; Exact sciences and technology; Lung - metabolism; Male; Other techniques and industries; Permeability; Pulmonary Edema - chemically induced; Pulmonary Edema - metabolism; Rats; Thiourea - analogs & derivatives
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1987.tb11284.x

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.