Charpie J R, Schreur K D, Papadopoulos S M, Webb R C
Department of Pediatric Cardiology, University of Michigan Medical School, Ann Arbor 48109-0622.
J Clin Invest. 1994 Mar;93(3):1339-43. doi: 10.1172/JCI117093.
Contractions to serotonin (5-HT) and endothelin-1 (ET-1) in infant (0-2 yr) and adult (38-71 yr) vertebral arteries were examined in the presence of either the cyclooxygenase inhibitor indomethacin or NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide production. In addition, endothelium-dependent relaxations to acetylcholine were characterized in arteries contracted with agonist. The results showed that: (a) Contractions of infant arteries to 5-HT or ET-1 decreased to 44 +/- 8% and 27 +/- 13%, respectively, within 10 min. Indomethacin or removal of endothelium abolished this decreased response, whereas L-NMMA had no effect. (b) Adult arteries produced sustained contractions to 5-HT or ET-1 that were unaffected by indomethacin, endothelium denudation, or L-NMMA. (c) Endothelium-dependent relaxations to acetylcholine were greater in infant than adult arteries and were abolished by indomethacin (but not L-NMMA) in infants and L-NMMA (but not indomethacin) in adults. Thus, endothelium-dependent responses in infant arteries are attenuated because of increased prostaglandin activity not observed in adult tissues. Additionally, there is an age-dependent change in the primary mechanism responsible for acetylcholine-induced vasodilation. Apparently, endothelium dependency of acetylcholine-induced relaxation is highly dependent on cyclooxygenase activity in the infant vertebral artery, but in the adult artery, nitric oxide is linked to the vasodilator response.
在存在环氧化酶抑制剂吲哚美辛或一氧化氮生成抑制剂NG-单甲基-L-精氨酸（L-NMMA）的情况下，研究了婴儿（0至2岁）和成人（38至71岁）椎动脉对血清素（5-HT）和内皮素-1（ET-1）的收缩反应。此外，还对用激动剂收缩的动脉中乙酰胆碱引起的内皮依赖性舒张进行了表征。结果表明：（a）婴儿动脉对5-HT或ET-1的收缩在10分钟内分别降至44±8%和27±13%。吲哚美辛或去除内皮可消除这种下降反应，而L-NMMA则无作用。（b）成人动脉对5-HT或ET-1产生持续收缩，不受吲哚美辛、内皮剥脱或L-NMMA的影响。（c）婴儿动脉中乙酰胆碱引起的内皮依赖性舒张大于成人动脉，吲哚美辛（而非L-NMMA）可消除婴儿动脉中的这种舒张，而L-NMMA（而非吲哚美辛）可消除成人动脉中的这种舒张。因此，婴儿动脉中的内皮依赖性反应因前列腺素活性增加而减弱，而成人组织中未观察到这种情况。此外，乙酰胆碱诱导血管舒张的主要机制存在年龄依赖性变化。显然，乙酰胆碱诱导舒张的内皮依赖性在婴儿椎动脉中高度依赖环氧化酶活性，但在成人动脉中，一氧化氮与血管舒张反应相关。
