Amitriptyline-induced release of endothelin-1 in isolated perfused and ventilated rat lungs

We have previously shown that tricyclic antidepressants can induce vaso- an d bronchoconstriction as well as oedema formation in isolated perfused lung s. This is an effect similar to that seen clinically in adult respiratory d istress syndrome. In order to investigate whether endothelin can be a media tor of this reaction, isolated perfused rat lungs were exposed to 0.1 mM am itriptyline via the pulmonary circulation, perfusate was collected and endo thelin-l present in the perfusate and lavage fluids was determined by radio immunoassay. A significant increase in perfusate concentration of endotheli n-1 was noted, with the highest release seen within the first 10 min, of ex posure. Histamine and thromboxane have also been proposed as mediators in i nduction of adult respiratory distress syndrome. However, no increased amou nts of these mediators were detected in the perfusate. Experiments where lu ngs were exposed to exogenous endothelin-1 (0.1-1 nmol), both via the perfu sate and via intratracheal instillation were conducted. Similar effects as observed with amitriptyline (0.1 mM) on lung function and perfusion flow we re detected. In conclusion, the detection of endothelin-l release in our lu ng model proposes a role for endothelin-1 in amitriptyline-induced vaso- an d bronchoconstriction and possibly in adult respiratory distress syndrome t ype reaction. Further studies with this model are interesting in order to e lucidate mechanisms behind the complex issue of adult respiratory distress syndrome-induction.