Assessment of nitric oxide formation during exercise

We measured the end-tidal plateau in exhaled NO concentration (CETNO) by chemiluminescence and calculated the product of (V) over dot E and CETNO ((V) over dot NO) in nine healthy subjects at rest and during three intensities of cycling exercise (30%, 60%, and 90% (V) over dot O(2)max), two levels of hyperventilation ((V) over dot E = 42.8 +/- 9.1 L/min and 84.2 +/- 6.6 L/min), and during breathing of hypoxic gas mixtures (five subjects, FIO2 = 14%) at rest and during exercise at 90% (V) over dot O(2)max. Immediately after each trial we also measured exhaled [NO] at constant expiratory flow rates ([NO](CF)) of 46 ml/s and 950 ml/s, utilizing added expiratory resistance to increase mouth pressure and close the velum (Silkoff and colleagues, Am. J. Respir. Grit. Care Med. 1997;155:260). CETNO decreased and (V) over dot NO increased above resting levels with increasing exercise intensity during hyperventilation and during hypoxic exercise (p < 0.05). [NO](CF), measured at either 46 ml/s or 950 ml/s, did not increase under any of the conditions investigated (exercise, hyperventilation, or hypoxia). Venous blood from seven of the subjects was sampled for the measurement of plasma [NO3-]. Resting plasma [NO3-] averaged 42.5 +/- 14.7 mu mol/L, with no change during exercise, hyperventilation, or hypoxia. On the basis of these results we conclude that reported increases in (V) over dot NO do not reflect an exercise-induced augmentation of systemic and/or airway NO production. Rather, the increases in (V) over dot NO during exercise or hyperventilation are a function of high airflow rates, which reduce the luminal [NO]. This decreases the concentration gradient for NO between the alveolar space and pulmonary capillary blood, which results in a decrease in the fraction of NO taken up by the blood and an increase in the volume of NO recovered in the exhaled air ((V) over dot NO).