Chronic nitric oxide synthase inhibition blunts endothelium-dependent function of conduit coronary arteries, not arterioles
Chronic nitric oxide synthase inhibition blunts endothelium-dependent function of conduit coronary arteries, not arterioles
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DOI：
10.1152/ajpheart.00899.2006
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发表时间：
2007-06-01
影响因子：
4.8
通讯作者：
Laughlin, M. Harold
中科院分区：
文献类型：
--
作者：
Ingram, David G.;Newcomer, Sean C.;Laughlin, M. Harold
目前的文献表明，慢性一氧化氮合酶（NOS）抑制对导管动脉与小动脉的内皮依赖性扩张（EDD）有不同的影响。因此，我们假设长期抑制 NOS 会损害猪左前降支 (LAD) 冠状动脉的 EDD，但不会损害冠状动脉。该研究包括三十九只雌性尤卡坦小型猪。动物饮用自来水或含有 N-G-硝基-L-精氨酸甲酯（L-NAME；100 mg/l）的水，分别形成对照组和慢性 NOS 抑制 (CNI) 组。治疗持续1-3个月（8.3+/-0.6mg.kg(-1.)day(-1)）。通过对 ADP（仅 LAD）和缓激肽 (BK) 的反应评估冠状动脉 LAD 和小动脉的体外 EDD，并通过对硝普钠 (SNP) 的反应评估内皮独立功能。慢性 NOS 抑制可减少冠状动脉 EDD 至 ADP 和 BK。将 LAD 环与 L-NAME 一起孵育会降低对照猪的 LAD 松弛反应，但不会降低 CNI 猪的 LAD 松弛反应，从而消除了组间差异。吲哚美辛 (Indo) 和磺胺苯唑孵育均不会显着影响 LAD 环对 ADP 或 BK 的松弛反应。 CNI 猪的冠状动脉对 SNP 表现出增强的松弛反应。与冠状动脉相比，CNI 猪的冠状动脉表现出对 BK 的 EDD 保留，并且对 SNP 的扩张反应没有增加。 L-NAME、Indo 和 L-NAME + Indo 孵育不会导致 BK 的小动脉扩张反应出现显着的组间差异。这些结果表明，虽然慢性 NOS 抑制会减少 LAD 环的 EDD（很可能是通过 NOS 依赖性机制），但它不会影响冠状动脉的 EDD。
Current literature suggests that chronic nitric oxide synthase (NOS) inhibition has differential effects on endothelium-dependent dilation (EDD) of conduit arteries vs. arterioles. Therefore, we hypothesized that chronic inhibition of NOS would impair EDD of porcine left anterior descending (LAD) coronary arteries but not coronary arterioles. Thirty-nine female Yucatan miniature swine were included in the study. Animals drank either tap water or water with N-G-nitro-L-arginine methyl ester (L-NAME; 100 mg/l), resulting in control and chronic NOS inhibition (CNI) groups, respectively. Treatment was continued for 1-3 mo (8.3 +/- 0.6 mg.kg(-1.)day(-1)). In vitro EDD of coronary LADs and arterioles was assessed via responses to ADP (LADs only) and bradykinin (BK), and endothelium-independent function was assessed via responses to sodium nitroprusside (SNP). Chronic NOS inhibition diminished coronary artery EDD to ADP and BK. Incubating LAD rings with L-NAME decreased relaxation responses of LADs from control pigs but not from CNI pigs such that between-group differences were abolished. Neither indomethacin (Indo) nor sulfaphenazole incubation significantly affected relaxation responses of LAD rings to ADP or BK. Coronary arteries from CNI pigs showed enhanced relaxation responses to SNP. In contrast to coronary arteries, coronary arterioles from CNI pigs demonstrated preserved EDD to BK and no increase in dilation responses to SNP. L-NAME, Indo, and L-NAME + Indo incubation did not result in significant between-group differences in arteriole dilation responses to BK. These results suggest that although chronic NOS inhibition diminishes EDD of LAD rings, most likely via a NOS-dependent mechanism, it does not affect EDD of coronary arterioles.