Maturational changes in endothelium-derived relaxing factor activity of ovine pulmonary arteries in vitro.
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.
Abman
S H
SH
Department of Pediatrics, University of Colorado School of Medicine, Denver 80262.
Chatfield
B A
BA
Rodman
D M
DM
Hall
S L
SL
McMurtry
I F
IF
D000109:Acetylcholine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000494:pharmacology; D005260:Female; D005865:Gestational Age; D066298:In Vitro Techniques; D007700:Kinetics; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D011247:Pregnancy; D011651:Pulmonary Artery / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D012756:Sheep; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D001120:Arginine; D000109:Acetylcholine