Developmental changes in endothelium-dependent relaxation of pulmonary arteries: role of EDNO and prostanoids.
We hypothesized that maturational changes in both prostaglandin and endothelium-derived nitric oxide (EDNO) activity contribute to developmental changes in endothelium-dependent relaxation of newborn pulmonary arteries. Responses to endothelium-dependent vasodilators acetylcholine, bradykinin, and calcium ionophore A-23187 were determined 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 EDNO synthesis with N omega-nitro-L-arginine (L-NNA), after inhibition of prostanoid synthesis with meclofenamate (Mec), or both modulators with both inhibitors. Endothelium-independent responses to sodium nitroprusside (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 tension occurred in 1m rings. L-NNA attenuated endothelium-dependent relaxation more in 2d rings, and SNP caused greater relaxation in 2d rings. However, Mec abolished all age-related differences by attenuating relaxation in 2d rings and constriction in 1m rings. These data suggest that developmental changes in 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.
O'Donnell
D C
DC
Department of Pediatrics, University of Maryland School of Medicine, Baltimore 21201, USA.
Tod
M L
ML
Gordon
J B
JB
D000818:Animals; D000831:Animals, Newborn; D004285:Dogs; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D024510:Muscle Development; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology*; D011651:Pulmonary Artery / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology*; D012756:Sheep; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase