Developmental changes in endothelium-dependent relaxation of pulmonary arteries: role of EDNO and prostanoids

O'Donnell, Denise C., Mary L. Tod, and John B. Gordon.Developmental changes in endothelium-dependent relaxation of pulmonary arteries: role of EDNO and prostanoids. J. Appl. Physiol. 81(5): 2013-2019, 1996.Wehypothesized that maturational changes in both prostaglandin andendothelium-derived nitric oxide (EDNO) activity contribute todevelopmental changes in endothelium-dependent relaxation of newbornpulmonary arteries. Responses to endothelium-dependent vasodilatorsacetylcholine, bradykinin, and calcium ionophore A-23187 weredetermined in phenylephrine-constricted third- and fourth-generation(1- to 2-mm-diameter) pulmonary artery rings from 2-day (2d)- and 1-mo(1m)-old lambs under control conditions (Con), after inhibition of EDNOsynthesis withN-nitro-L-arginine(L-NNA), after inhibition ofprostanoid synthesis with meclofenamate (Mec), or both modulators withboth inhibitors. Endothelium-independent responses to sodiumnitroprusside (SNP) were also measured in Con rings.Endothelium-dependent relaxation was greater in 2d than 1m Con rings,particularly at high concentrations when an increase in tensionoccurred in 1m rings. L-NNAattenuated endothelium-dependent relaxation more in 2d rings, and SNPcaused greater relaxation in 2d rings. However, Mec abolished allage-related differences by attenuating relaxation in 2d rings andconstriction in 1m rings. These data suggest that developmental changesin endothelium-dependent responses of ovine pulmonary artery rings reflect both a decrease in EDNO activity and maturational differences in the relative influence of dilator and constrictor prostanoids.