Maturational modulation of endothelium-dependent vasodilatation in ovine cerebral arteries.
Maturational modulation of endothelium-dependent vasodilatation in ovine cerebral arteries.
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绵羊脑动脉内皮依赖性血管舒张的成熟调节。
DOI：
10.1152/ajpregu.00427.2004
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Pearce,WilliamJ
中科院分区：
文献类型：
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作者：
Williams,JamesM;Hull,AndrewD;Pearce,WilliamJ
为了验证成熟增强脑动脉内皮血管舒张功能的假设，我们在25只新生羔羊（3-7天）和23只成年绵羊的颈动脉和脑动脉中检测了ADP和A-23187的松弛反应。成熟显著提高了A-23187的pd2值（新生儿范围：4.9±0.3至5.4±0.3；成人范围：6.0±0.2至7.1±0.2），A-23187的最大血管扩张剂反应提高了10-18%。相比之下，成熟使ADP的最大反应降低了5-25%，而pD2没有变化。10 μM吲哚美辛不影响血管内皮依赖性舒张的幅度，而100 μM -硝基精氨酸甲酯/l-硝基精氨酸几乎消除了血管内皮依赖性舒张，表明一氧化氮（NO）是血管内皮依赖性舒张剂的主要作用。成熟也适度降低了颈动脉（32%）和脑动脉（26%）内皮NO合成酶（eNOS）的丰度。总之，这些发现强化了受体偶联内皮活化受到严格调节的观点，并可能抵消最大内皮血管扩张剂容量的潜在变化。这种能力，反过来，似乎随着出生后年龄增加，尽管内皮细胞的大小和血管壁体积的主要增长和扩大。在绵羊脑动脉中，内皮血管扩张能力似乎完全依赖于eNOS活性，而不依赖于环氧化酶活性。反过来，eNOS活性似乎是由独立于eNOS丰度变化的机制在出生后调节的。
To address the hypothesis that maturation enhances endothelial vasodilator function in cerebral arteries, relaxant responses to ADP and A-23187 were determined in ovine carotid and cerebral arteries harvested from 25 newborn lambs (3–7 days) and 23 adult sheep. Maturation significantly increased pD2values for A-23187 (newborn range: 4.9 ± 0.3 to 5.4 ± 0.3; adult range: 6.0 ± 0.2 to 7.1 ± 0.2) and the maximal vasodilator response to A-23187 by 10–18%. In contrast, maturation decreased maximum responses to ADP by 5–25% with no change in pD2. The magnitudes of endothelium-dependent relaxation were not affected by 10 μM indomethacin but were virtually abolished by 100 μMNG-nitro-l-arginine methyl ester/l-nitro arginine, indicating that nitric oxide (NO) is the primary endothelium-dependent vasodilator in these arteries. Maturation also modestly decreased endothelial NO synthase (eNOS) abundance in both carotid (32%) and cerebral (26%) arteries. Together, these findings reinforce the view that receptor coupling to endothelial activation is tightly regulated and may offset underlying changes in maximal endothelial vasodilator capacity. This capacity, in turn, appears to increase with postnatal age despite major growth and expansion of endothelial cell size and vascular wall volume. In ovine cerebral arteries, endothelial vasodilator capacity appears completely dependent on eNOS activity but not on cyclooxygenase activity. In turn, eNOS activity appears to be postnatally regulated by mechanisms independent of changes in eNOS abundance alone.