Maturational changes in ovine pulmonary vascular responses to inhaled nitric oxide

Developmental changes in modulation of pulmonary vasomotor tone by endothel ium-derived nitric oxide (EDNO) may reflect maturational differences in end othelial synthesis of and/or vascular smooth muscle response to nitric oxid e. This study sought to determine whether pulmonary vascular sensitivity an d responsiveness to nitric oxide change during newborn development, and whe ther this is related to changes in guanylate cyclase activity. Pulmonary ar tery dose-responses to inhaled nitric oxide (iNO, 0.25-100 parts per millio n) were measured in hypoxic, indomethacin-treated, isolated lungs from 1-da y (1-d)- and 1-month (1-m)-old lambs. The lungs of 1-m-old lambs were venti lated with 4% (oxygen) O-2, and lungs of 1-d-old lambs were ventilated with either 4% or 7% O-2 in order to achieve similar stimuli or vasomotor tone. Cyclic guanosine monophosphate (cGMP) concentrations in the perfusate were measured at iNO concentrations of 0, 5, and 100 parts per million (ppm). B asal and stimulated pulmonary guanylate cyclase activity was also measured in lung extracts in vitro. The effects of iNO were similar in both 1-d groups, even though baseline hy poxic tone was significantly higher in 1-d lungs ventilated with 4% O-2 tha n with 7% O-2. Furthermore, both the 1-d 7% O-2 and 1-d 4% O-2 lungs exhibi ted greater responsiveness and sensitivity to iNO than 1-m lungs. Perfusate cGMP concentrations and soluble guanylate cyclase activity were higher und er stimulated than basal conditions, but neither differed statistically bet ween 1 d and 1 m. These data suggest that pulmonary vascular responsiveness and sensitivity t o nitric oxide decrease with age, but the mechanisms underlying these matur ational changes require further investigation. (C) 1999 Wiley-Liss, Inc.