The Role of N Omega-nitro-L-arginine in Modulation of Pulmonary Vascular Tone in the Maturing Newborn Pig

Current therapeutic modalities for treatment of newborn pulmonary hypertensive crisis include but are not limited to the administration of nitric oxide (endothelium-derived relaxing factor). However, few data are available on the role of endogenously produced endothelium-derived relaxing factor in the modulation of pulmonary vascular tone in the neonate. In the current study, we investigated the acute effects of N omega-nitro-L-arginine (a potent competitive inhibitor of endothelium-derived relaxing factor synthase) on the pulmonary vasculature of anesthesized open-chest 48-hour-old (n = 8) and 2-week-old (n = 7) Yorkshire pigs. After baseline data were acquired, all animals received a 10 mg/kg per minute infusion of N omega-nitro-L-arginine for 10 minutes. To discern distal and proximal pulmonary arterial vessel changes, input mean and characteristic impedance were respectively determined. Pulmonary vascular resistance was also calculated (units determined in dyne.sec.cm-5 plus or minus the standard error of the mean). Results showed N omega-nitro-L-arginine infusion did not significantly alter baseline pulmonary arterial pressure (22,370 +/- 1473 dyne/cm2), pulmonary vascular resistance (5171 +/- 805 dyne.sec.cm-5), input impedance (6343 +/- 806 dyne.sec.cm-5), or characteristic impedance (2073 +/- 418 dyne.sec.cm-5) in 48-hour-old pigs. In 2-week-old pigs, infusion of N omega-nitro-L-arginine elevated pulmonary arterial pressure (18,162 +/- 1415 dyne/cm2 versus 23,838 +/- 1810 dyne/cm2, p = 0.015), pulmonary vascular resistance (810 +/- 137 dyne.sec.cm-5 versus 1519 dyne.sec.cm-5, p = 0.030), and input impedance (2302 +/- 251 dyne.sec.cm-5 versus 2900 +/- 255 dyne.sec.cm-5, p = 0.018). Characteristic impedance was not altered in 2-week-old pigs. These data indicate that N omega-nitro-L-arginine infusion resulted in pulmonary arteriolar vasoconstriction in 2-week-old pigs, but not in 48-hour-old pigs. This finding suggests that endothelium-derived relaxing factor does not modulate basal pulmonary arteriolar tone during the early newborn period, but does play a significant role in 2-week-old pigs. These data also suggest that the functional role for endothelium-derived relaxing factor is confined to the distal arteriolar pulmonary bed and does not extend to the larger proximal arterial vessels.