DEVELOPMENTAL-CHANGES IN ENDOTHELIUM-DEPENDENT RELAXATION OF PULMONARY-ARTERIES - ROLE OF EDNO AND PROSTANOIDS

We hypothesized that maturational changes in both prostaglandin and en dothelium-derived nitric oxide (EDNO) activity contribute to developme ntal changes in endothelium-dependent relaxation of newborn pulmonary arteries. Responses to endothelium-dependent vasodilators acetylcholin e, bradykinin, and calcium ionophore A-23187 were determined in phenyl ephrine-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 EDNO synthesis with N-o mega-nitro-L-arginine (L-NNA), after inhibition of prostanoid synthesi s with meclofenamate (Mec), or both modulators with both inhibitors. E ndothelium-independent responses to sodium nitroprusside (SNP) were al so measured in Con rings. Endothelium-dependent relaxation was greater in 2d than Im Con rings, particularly at high concentrations when an increase in tension occurred in Im rings. L-NNA attenuated endothelium -dependent relaxation more in 2d rings, and SNP caused greater relaxat ion in 2d rings. However, Mec abolished all age-related differences by attenuating relaxation in 2d rings and constriction in Im rings. Thes e data suggest that developmental changes in endothelium-dependent res ponses of ovine pulmonary artery rings reflect both a decrease in EDNO activity and maturational differences in the relative influence of di lator and constrictor prostanoids.