EXHALED NITRIC-OXIDE IN ISOLATED PIG LUNGS

Endothelium-derived nitric oxide (NO) is an important regulator of vas cular resistance. Low concentrations of NO have been recorded in the e xhaled breath of spontaneously breathing animals and humans, To determ ine 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 chemilumine scence 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 p erfusate, 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. Vasoc onstriction with the thromboxane analogue U-46619 (10(-9) M) raised PV R to 31.7 +/- 6.8 mmHg.l(-1) min but did not decrease NO levels from b aseline. Subsequent addition of acetylcholine (10(-6) M) lowered PVR t o 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 e ster (10(-5) M), to four lungs caused a rise in PVR to 43.0 +/- 7.0 mm Hg.l(-1) min and a decrease in NO to 1.5 +/- 1.0 ppb. Addition of auto logous blood to the perfusate of four lungs caused no change in PVR fr om 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 pulmo nary vascular endothelium may contribute to the NO found in exhaled ai r.