O'Donnell D C, Tod M L, Gordon J B
Department of Pediatrics, University of Maryland School of Medicine, Baltimore 21201, USA.
J Appl Physiol (1985). 1996 Nov;81(5):2013-9. doi: 10.1152/jappl.1996.81.5.2013.
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.
我们推测，前列腺素和内皮源性一氧化氮（EDNO）活性的成熟变化促成了新生肺动脉内皮依赖性舒张功能的发育变化。在对照条件下（Con），用Nω-硝基-L-精氨酸（L-NNA）抑制EDNO合成后，用甲氯芬那酸（Mec）抑制前列腺素合成后，或用两种抑制剂同时抑制两种调节剂后，测定了来自2日龄（2d）和1月龄（1m）羔羊的苯肾上腺素收缩的第三代和第四代（直径1至2毫米）肺动脉环对内皮依赖性血管舒张剂乙酰胆碱、缓激肽和钙离子载体A-23187的反应。还在Con环中测量了对硝普钠（SNP）的非内皮依赖性反应。在2d的Con环中，内皮依赖性舒张比1m的Con环更大，特别是在高浓度时，此时1m环中张力增加。L-NNA在2d环中更能减弱内皮依赖性舒张，而SNP在2d环中引起更大的舒张。然而，Mec通过减弱2d环中的舒张和1m环中的收缩，消除了所有与年龄相关的差异。这些数据表明，绵羊肺动脉环内皮依赖性反应的发育变化反映了EDNO活性的降低以及扩张性和收缩性前列腺素相对影响的成熟差异。
