Arginine analogs, such as N^G-monomethyl-L-arginine (L-NMMA) or N^G-nitro-L-arginine (L-NA), are commonly used as inhibitors of the synthesis of endothelium-derived relaxing factor, nitric oxide (NO). However, their effect on NO levels is rarely measured. Using a chemiluminescence assay for NO, we found that L-NMMA (but not L-NA) enhanced, rather than reduced, NO synthesis in pulmonary arterial and aortic rings. Thus L-NMMA is a partial agonist for NO synthesis.

Many studies of hypoxic pulmonary vasoconstriction use oxygen scavenger, dithionite, rather than authentic hypoxia. In this study we demonstrated that using dithionite for this purpose is incorrect, because dithionite causes only very transient decrease of PO2 in isolated ventilated perfused lungs and elicits a massive burst of radical formation (Figure). This is in sharp contrast to ventilatory hypoxia, which actually reduces radical synthesis in this preparation (Figure).

Unlike ventilatory hypoxia (left), dithionite (right) causes a massive outburst of radical production and only a transient decrease in PO2 in isolated perfused rat lungs. Isolated rat lungs were perfused with Krabs-albumin solution at constant flow rate (0.04 ml/min/g body weight), so that increases in pulmonary arterial (PA) pressure reflect vasoconstriction. Radicals production was measured as luminol-enhanced chemiluminescence.

After nitric oxide (NO), an important endogenously produced vasodilator, was found in human breath, it was hoped for some time that its measurement could be used for diagnostics of pulmonary vascular disease. We therefore decided to find out what is the main source of NO in the human breath. Using the chemiluminescence assay of NO, we found the main source of NO in the human breath to be the nose, while the contribution from the distal airways is negligible (Figure).

Concentration of nitric oxide (NO) in exhaled air collected in the nose is much higher that in air sampled in the mouth, trachea, carina and distal airway(n=7). Samples from the trachea are from 9 intubated patients, while all the other values are from 7 patients before (nose, mouth) and during (carina, distal airway) bronchoscopic examination. The data are the means±SEM. *P<0.001 vs. all other locations.

In this study we found that, in contrast to other models of hypercholesterolemia, endothelium-dependent vasodilation is not impaired in a genetically hyperlipidemic (JCR:LA-cp) strain of rats.