EXHALED NITRIC-OXIDE IN ISOLATED PIG LUNGS

Endothelium-derived nitric oxide (NO) is an important regulator of vascular resistance. Low concentrations of NO have been recorded in the exhaled breath of spontaneously breathing animals and humans, To determine whether NO synthesis in the lung contributes to the NO measured in the breath, we measured the concentration of NO in the exhaled air of isolated perfused and ventilated porcine lungs by using a chemiluminescence method. With NO-free normoxic ventilation (21% O-2-5% CO2-74% N-2) of eight porcine lungs perfused with a Krebs-dextran and albumin perfusate, baseline exhaled NO was 5.8 +/- 1.8 parts per billion (ppb) and pulmonary vascular resistance (PVR) was 8.9 +/- 1.8 mmHg.l(-1) min. Hypoxic ventilation (5% O-2-5% CO2-90% N-2) caused a fall in NO to 3.6 +/- 1.8 ppb and a rise in PVR to 13.6 +/- 3.6 mmHg.l(-1) min. Vasoconstriction with the thromboxane analogue U-46619 (10(-9) M) raised PVR to 31.7 +/- 6.8 mmHg.l(-1) min but did not decrease NO levels from baseline. Subsequent addition of acetylcholine (10(-6) M) lowered PVR to 22.1 +/- 4.5 mmHg.l(-1) min and increased exhaled NO to 7.0 +/- 2.0 ppb. Addition of a NO synthase inhibitor, NG-nitro-L-arginine methyl ester (10(-5) M), to four lungs caused a rise in PVR to 43.0 +/- 7.0 mmHg.l(-1) min and a decrease in NO to 1.5 +/- 1.0 ppb. Addition of autologous blood to the perfusate of four lungs caused no change in PVR from baseline but decreased exhaled NO to 2.7 +/- 0.5 ppb. In four lungs perfused at raised outflow pressure, interstitial edema decreased NO levels from 3.5 +/- 1.2 to 0.9 +/- 0.3 ppb. We conclude that the pulmonary vascular endothelium may contribute to the NO found in exhaled air.