Maturation alters the pulmonary arterial response to hypoxia and inhaled nitric oxide in the presence of endothelial dysfunction.

Surgical intervention in ever younger patients has led to a new appreciation of the unique physiology of the neonate. Specifically, newborn patients may respond very differently to hypoxic episodes and subsequent treatment with inhaled nitric oxide than older infants. In the current study, we examined differences in the pulmonary arterial response to hypoxia and inhaled nitric oxide in 48-hour-old (n = 8) and 14-day-old (n = 8) Yorkshire pigs in a model of nitric oxide synthase inhibition, as might be seen with endothelial dysfunction. Data were acquired after treatment with the nitric oxide synthase inhibitor N omega-nitro-L-arginine during hypoxia (inspired oxygen fraction = 0.10) and during inhalation of nitric oxide (100 ppm). Input mean impedance, reflecting distal arteriolar vasoconstriction, and characteristic impedance, reflecting proximal arterial geometry and distensibility, were calculated. The modulus of elasticity, a measure of the "stiffness" of the proximal vessels, was also calculated. Hypoxia caused a large increase in input mean impedance in both 48-hour-old and 14-day-old pigs (4826 +/- 272 versus 8744 +/- 488 dyne.cm.sec-5 and 3129 +/- 73 versus 6000 +/- 134 dyne.cm.sec-5, respectively; p = 0.0078). Characteristic impedance was not altered in the younger animals (1171 +/- 76 dyne.cm.sec-5) but increased in the older animals (419 +/- 15 versus 797 +/- 20 dyne.cm.sec-5. p = 0.0078). Older animals also experienced an increase in the modulus elasticity (1.92E06 +/- 3.2E05 versus 1.05E07 +/- 3.9E05 dyne/cm2, p = 0.0078). These data show that inhibited nitric oxide production, as might be seen in endothelial dysfunction, potentiates the profound hypoxic vasoconstriction observed at the level of the distal pulmonary arterioles in both neonatal and infant animals. In contrast, only older animals had a stiffening of the larger, more proximal vessels with hypoxia. In both age groups, inhaled nitric oxide effectively reduced the increases in impedance.