Cyclo-oxygenase-2 inhibition and endothelium-dependent vasodilation in younger vs. older healthy adults.
Cyclo-oxygenase-2 inhibition and endothelium-dependent vasodilation in younger vs. older healthy adults.
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DOI：
10.1111/bcp.12397
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发表时间：
2014-10
影响因子：
3.4
通讯作者：
J. Eisenach;Leah R. Gullixson;Alexander R. Allen;S. Kost;W. Nicholson
中科院分区：
文献类型：
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作者：
J. Eisenach;Leah R. Gullixson;Alexander R. Allen;S. Kost;W. Nicholson
目的 内皮功能障碍的一个主要特征是内皮依赖性血管舒张减少，这在衰老过程中可能是由于内皮前列环素或一氧化氮 (NO) 或两者的产生减少所致。方法 我们在 12 名年轻人（年龄 18-38 岁，六名女性）和 12 名老年健康成年人（年龄 55-73 岁，六名绝经后女性）中测试了这一假设。内皮依赖性血管舒张通过口服塞来昔布（400）抑制环加氧酶-2（COX-2）之前和之后90分钟对动脉内乙酰胆碱（ACh）（0.5、1.0、2.0、4.0μg dl（-1）前臂组织min（-1））的前臂血管电导（FVC）反应进行评估mg），然后添加动脉内 N(G)-单甲基-1 精氨酸乙酸酯 (L-NMMA) 抑制内皮 NO 合酶。结果 衰老与 ACh 的 FVC 反应显着降低相关（P = 0.009，年龄-剂量相互作用；衰老时最高剂量 FVC ± SEM：11.2 ± 1.4 对比年轻时：17.7 ± 2.4 单位，P = 0.02）。塞来昔布不会降低任何组的静息用力肺活量或对乙酰胆碱的反应。 L-NMMA 显着降低了所有组中的静息 FVC 和对 ACh 的反应，并且 L-NMMA 后的绝对 FVC 值在各组之间相似。结论 在健康血压正常的年轻人和老年人中，前列环素对乙酰胆碱介导的血管舒张作用很小，但血管舒张的一氧化氮成分随着年龄的增长而减少。在临床背景下，这些发现表明，急性服用抑制前列环素的药物（即 COX-2 抑制剂）会对健康人产生适度的血管后果。需要进行更多研究来测试长期使用 COX-2 药物是否会减少有或没有心血管危险因素的老年人的内皮依赖性血管舒张。
AIM A major feature of endothelial dysfunction is reduced endothelium-dependent vasodilation, which in ageing may be due to decreased production of endothelial prostacyclin, or nitric oxide (NO), or both. METHOD We tested this hypothesis in 12 younger (age 18-38 years, six women) and 12 older healthy adults (age 55-73 years, six post-menopausal women). Endothelium-dependent vasodilation was assessed by the forearm vascular conductance (FVC) response to intra-arterial acetylcholine (ACh) (0.5, 1.0, 2.0, 4.0 μg dl(-1) forearm tissue min(-1) ) before and 90 min after inhibition of the enzyme cyclo-oxygenase-2 (COX-2) with oral celecoxib (400 mg), followed by the addition of endothelial NO synthase inhibition with intra-arterial N(G) -monomethyl-l arginine acetate (L-NMMA). RESULTS Ageing was associated with a significantly reduced FVC response to ACh (P = 0.009, age-by-dose interaction; highest dose FVC ± SEM in ageing: 11.2 ± 1.4 vs. younger: 17.7 ± 2.4 units, P = 0.02). Celecoxib did not reduce resting FVC or the responses to ACh in any group. L-NMMA significantly reduced resting FVC and the responses to ACh in all groups, and absolute FVC values following L-NMMA were similar between groups. CONCLUSION In healthy normotensive younger and older adults, there is minimal contribution of prostacyclin to ACh-mediated vasodilation, yet the NO component of vasodilation is reduced with ageing. In the clinical context, these findings suggest that acute administration of medications that inhibit prostacyclin (i.e. COX-2 inhibitors) evoke modest vascular consequences in healthy persons. Additional studies are necessary to test whether chronic use of COX-2 medications reduces endothelium dependent vasodilation in older persons with or without cardiovascular risk factors.