Effect of exogenous and endogenous nitric oxide on the airway and tissue components of lung resistance in the newborn piglet

Despite widespread reports of the vasodilatory actions of nitric oxide (NO), little is known of the relaxant effect of NO on newborn airways or lung parenchymal structures. We studied the effects of inhaled NO at 20, 40, and 80 ppm on lung (R-1), tissue (R-ti), and airway (R-aw) resistance in 13 2-5-d-old anesthetized, ventilated, open-chested piglets. R-1 was measured from transpulmonary pressure and air flow. R-ti was measured by alveolar capsules, and Raw was calculated as the difference betwen R-1 and R-ti. Any given concentration of inhaled NO (20, 40, or 80 ppm) significantly decreased R-1 (p < 0.001), R-ti (p < 0.001), and Raw (p < 0.05). In addition, blockade of endogenous NO with 30 mg/kg N omega-nitro-L-arginine methyl ester (L-NAME) given i.v. in 12 piglets significantly increased R-ti and R-1 with variable changes in R-aw, and caused a decrease in dynamic compliance. Readministration of NO to eight piglets induced a significant decrease in R-1 and R-ti at 20 and 80 ppm, whereas R-aw significantly decreased only at 80 ppm, whereas R-aw significantly decreased only at 80 ppm. Pulmonary arterial pressure decreased after exposure to inhaled NO and increased after L-NAME administration. Systemic arterial pressure was unaffected by inhaled NO but increased after L-NAME administration. Our results indicate that R-1, R-aw, and R-ti are reduced by exogenous NO, suggesting NO-mediated airway smooth muscle relaxation throughout the newborn lung. In contrast, blockade of endogenous NO significantly increases only R-ti suggesting a physiologic role for endogenous NO in regulation of peripheral contractile elements. We speculate that NO-mediated modulation of resistance in pulmonary parenchyma may serve to regulate the balance of ventilation and perfusion and resultant gas exchange in the lungs during early postnatal development.