Effect of age on kinetics of nitric oxide release in rat aorta and pulmonary artery
Effect of age on kinetics of nitric oxide release in rat aorta and pulmonary artery
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DOI：
10.1172/jci118872
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发表时间：
1996-08-15
影响因子：
15.9
通讯作者：
Luscher, TF
中科院分区：
文献类型：
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作者：
Tschudi, MR;Barton, M;Luscher, TF
衰老是血管疾病的一个重要决定因素。内皮源性一氧化氮（NO）作为血管扩张剂和血小板功能抑制剂具有保护作用。本研究旨在直接测量长时间老化对离体血管内皮MO释放的影响，并描绘体循环和肺循环之间的差异。采用5-6月龄（青年）、18-19月龄（中年）和32-33月龄（老年）血压正常的雌性大鼠的主动脉和肺动脉。血压和血浆雌二醇-17 β（E（2））保持不变。在离体血管中，NO释放由受体非依赖性激动剂钙离子载体A23187（10 μ mol/L）诱导，并使用卟啉微传感器在血管内皮表面上原位测量。中老年大鼠主动脉起始NO释放速率和峰值NO浓度降低（P < 0.0006 vs.年轻大鼠，n = 6）。此外，内皮依赖性舒张钙离子载体和乙酰胆碱，（10（-10）~ 10（-5）mol/L），老年大鼠睾丸组织中的β-淀粉样蛋白含量也明显低于青年大鼠（n = 6，P < 0.05）。NO释放的起始速率和峰值浓度与对钙离子载体A23187的最大舒张作用呈显著正相关（r = 0.916，P < 0.0018和r = 0.961，P < 0.0001，n = 7）。然而，在肺动脉中，NO释放的初始速率以及峰值NO浓度并不随年龄而降低（每个年龄组n = 6，NS）。在所有年龄组（n = 6，NS）的两条血管中，NO释放不受超氧化物歧化酶的影响。因此，衰老特异性地降低了从主动脉而不是肺动脉释放内皮NO的初始速率和峰值浓度，表明NO产生减少。由于动脉压不随年龄变化，主动脉长期暴露于比肺动脉更高的压力和/或脉动可能是原因。这似乎很重要，因为NO通过防止血管收缩、血栓形成和动脉粥样硬化发挥保护作用。
Aging is an important determinant of vascular disease. Endothelium-derived nitric oxide (NO) is protective as a vasodilator and inhibitor of platelet function, This study was designed to directly measure effects of prolonged aging on endothelial MO release in isolated blood vessels and to delineate differences between the systemic and pulmonary circulation. Aortas and pulmonary arteries from 5-6-mo-old (young), 18-19-mo-old (middle-aged), and 32-33-mo-old (old) normotensive female rats were used, Blood pressure and plasma estradiol-17 beta (E(2)) remained unchanged. In isolated blood vessels, NO release was induced by the receptor-independent agonist calcium ionophore A23187 (10 mu mol/liter) and measured in situ on the endothelial surface of vessels using a porphyrinic microsensor, In vessels suspended in organ chambers isometric tension was recorded. Tn the aorta, the initial rate of NO release and peak NO concentration (sic) reduced in middle-aged and old rats (P < 0.0006 vs. young rats, n = 6), Furthermore, endothelium-dependent relaxations to calcium ionophore and acetylcholine (both 10(-10)-10(-5) mol/liter) were also reduced in aortas from old as compared with young rats(n = 6, P < 0.05). The initial rate of NO release and peak NO concentration significantly correlated with maximal relaxation to calcium ionophore A23187 (correlation coefficients r = 0.916, P < 0.0018 and r = 0.961, P < 0.0001, respectively, n = 7). In pulmonary arteries, however, the initial rate of NO release as well as peak No concentration did not decrease with age (n = 6 for each age group, NS). In both blood vessels, the NO release was unaffected by superoxide dismutase in all age groups (n = 6, NS). Thus, aging specifically reduces initial rate and peak concentrations of endothelial NO release from aorta but not pulmonary artery indicating reduced NO production. As arterial pressure did not change with aging, the chronic exposure of the aorta to higher pressure and/or pulsatility than in the pulmonary artery may be the cause. This appears important as NO plays a protective role by preventing vasoconstriction, thrombosis and atherosclerosis.