Endothelin-1-induced increases in microvascular permeability in isolated, perfused rat lungs requires leukocytes and plasma.

Effect of endothelin-1 (ET-1) (10(-8) M) on pulmonary microvascular permeability was examined in isolated rat lungs perfused with blood or various blood components. Microvascular permeability was assessed by measuring fluid filtration rate (FFR) in lungs pretreated with papaverine in order to prevent changes in vascular smooth muscle tone. ET-1 significantly increased FFR (131.0 +/- 10.1 mg/min, P < 0.01) after perfusion with blood for 60 min. In lungs perfused with leukocytes resuspended in plasma, ET-1 increased FFR significantly both 30 min (40.4 +/- 11.4 mg/min, P < 0.01) and 60 min (97.4 +/- 14.5 mg/min, P < 0.01) after it was added to the perfusate. Heat inactivation (56 degrees C; 1 hr) of plasma did not attenuate this effect of ET-1 (94.4 +/- 25.1 mg/min, P < 0.01). When lungs were perfused with leukocytes resuspended in Krebs Ringer albumin instead of plasma, or with plasma only, ET-1 did not cause any change in FFR. In conclusion, ET-1 increases microvascular permeability in isolated blood-perfused rat lungs. The effect is critically dependent on the presence of leukocytes and plasma components other than complement.