Cyclooxygenase Products Contribute to Endothelin-induced Pulmonary Hypertension and Altered Lung Mechanics in Sheep

Endothelins have potent biological effect in vivo which may, in part, be mediated by stimulation of cyclooxygenase metabolism of arachidonic acid, We administered endothelins (ETs) intravenously to chronically instrumented awake sheep with and without pretreatment with meclofenamate (n = 8). 30 mu g doses of ET-1, ET-2, and ET-3 caused similar degrees of acute elevation of pulmonary artery pressure (P-PA), reduction of the dynamic compliance of the lungs (C-dyn), and increases in lung lymph flow, Pretreatment with meclofenamate inhibited the rise in P-PA and reduction in C(dyn), but had no effect on lung lymph how, We conclude that the biological effects of the endothelins on P-PA and C-dyn, but not lung fluid balance, are mediated in part by cyclooxygenase products of arachidonic acid metabolism. (C) 1997 Academic Press Limited.