Sustained effects of endothelin-1 on rabbit, dog, and rat pulmonary circulations

Effects of endothelin-1 (10^-8 M) on the pulmonary vascular resistance-compliance profile were examined in isolated blood-perfused rabbit, dog, and rat lungs using occlusion techniques. Capillary permeability was assessed by filtration coefficient (K(fc)). Cyclooxygenase products were assessed by radioimmunoassay. In rabbit lungs, endothelin-1 increased all resistances except large vein; ibuprofen reversed the constriction. Endothelin-1 decreased total vascular compliance (C(T)), which was reversed by ibuprofen. Cyclooxygenase products were unchanged by endothelin-1 or endothelin-1 plus ibuprofen. In dog lungs, large vein resistance increased after endothelin-1; ibuprofen increased large arterial resistance. Endothelin-1 decreased C(T) and middle compartment compliance, and endothelin-1 plus ibuprofen decreased large vessel compliance (C(LV)). Ibuprofen reversed the endothelin-1 increase in plasma 6-oxo-prostaglandin F(1α). In rat lungs, ibuprofen reversed the endothelin-1 increase in small arterial resistance. Endothelin-1 decreased C(LV), and endothelin-1 plus ibuprofen returned the compliance to baseline values. Ibuprofen potentiated the endothelin-1 increase in plasma prostanoids. Endothelin-1 plus indomethacin increased vascular resistance and blocked prostaglandin production. K(fc) was increased only in rat lung after endothelin-1 plus ibuprofen. In summary, endothelin-1 increased pulmonary vascular resistance, which was attenuated by prostacyclin in dogs and rats. In rabbits, the resistance increase was reversed by ibuprofen.