Maturational changes in endothelium-derived relaxing factor activity of ovine pulmonary arteries in vitro

Abstract

To examine mechanisms underlying fetal pulmonary vascular vasodilator responses and maturational changes in endothelial function, we studied effects of endothelium-dependent (acetylcholine, ACh: adenosine diphosphate, ADP; and A23187) and -independent (sodium nitroprusside, SNP) vasodilators on tone of small (third generation) pulmonary artery rings isolated from late-gestation fetal, newborn, and adult sheep. Changes in isometric force of phenylephrine-contracted rings were measured after the cumulative addition of vasodilators in baths aerated with 21% O2 and 5% CO2. Pulmonary artery rings from fetal lambs demonstrated minimal relaxation to ACh, ADP, and A23187, achieving only 17 +/- 3, 14 +/- 5, and 23 +/- 8% relaxation, respectively. In contrast, fetal rings relaxed completely (100%) to SNP. Rings from newborn and adult animals had significantly greater maximal relaxation in response to ACh. ADP, and A23187 than fetal rings (at least P less than 0.05 for each comparison with fetal rings), but responses to SNP were not different. Hemoglobin (10(-5) M), an inhibitor of endothelium-derived relaxing factor, caused less augmentation of phenylephrine contraction in fetal than adult pulmonary artery rings (11 +/- 4% vs. 49 +/- 8%; P less than 0.01). We conclude that in comparison with pulmonary artery rings from postnatal animals, fetal pulmonary artery rings have diminished endothelium-derived relaxation factor activity. We speculate that maturational changes in endothelial cell function contribute to ontogenetic differences in pulmonary vasoreactivity.