Neuronal nitric oxide synthase and human vascular regulation.
Neuronal nitric oxide synthase and human vascular regulation.
复制标题
DOI：
10.1016/j.tcm.2010.02.007
复制
发表时间：
2009-11
影响因子：
9.3
通讯作者：
Shah, Ajay M.
中科院分区：
文献类型：
--
作者：
Melikian, Narbeh;Seddon, Michael D.;Casadei, Barbara;Chowienczyk, Philip J.;Shah, Ajay M.
血管血流及其在不同血管床之间的分布受微血管张力变化的调节。一氧化氮（NO）在静息状态下以及当血流响应于激动剂刺激或增加的剪切应力而增加时，在血管张力的局部旁分泌调节中起关键作用。传统的观念，即内皮NO合酶（eNOS）衍生的NO是主要负责这两种效果已受到挑战的第一次在人类的研究与神经元NOS（nNOS）的选择性抑制剂，S-甲基-L-硫代瓜氨酸（SMTC）。这些研究表明，SMTC导致正常人前臂和冠状动脉循环中的基础血流量减少（由l-精氨酸逆转），而不影响由乙酰胆碱、P物质或增加的剪切应力引起的eNOS介导的血管舒张。S-甲基-l-硫代瓜氨酸也抑制精神压力诱导的血管舒张。这些结果是一致的一个显着的身体的实验研究表明，nNOS在其他物种的血管紧张度的局部调节中起着重要的作用，独立的nNOS衍生的NO在中枢神经系统的影响。这些新出现的数据表明，eNOS和nNOS在人体微血管张力的生理局部调节中具有不同的作用，并为进一步详细研究nNOS和eNOS在人类疾病中血管调节的相对贡献铺平了道路。
Vascular blood flow and its distribution among different vascular beds are regulated by changes in microvascular tone. Nitric oxide (NO) plays a key role in the local paracrine regulation of vessel tone both under resting conditions and when blood flow increases in response to agonist stimulation or increased shear stress. The conventional notion that endothelial NO synthase (eNOS)-derived NO is largely responsible for both effects has been challenged by first-in-human studies with a selective inhibitor of neuronal NOS (nNOS), S-methyl-l-thiocitrulline (SMTC). These studies reveal that SMTC causes a reduction in basal blood flow in the normal human forearm and coronary circulations (that is reversed by l-arginine), without affecting the eNOS-mediated vasodilatation elicited by acetylcholine, substance P, or increased shear stress. S-methyl-l-thiocitrulline also inhibits mental stress-induced vasodilatation. These results are consistent with a significant body of experimental studies suggesting that nNOS plays an important role in the local regulation of vessel tone in other species, independent of the effects of nNOS-derived NO in the central nervous system. These emerging data suggest that eNOS and nNOS have distinct roles in the physiologic local regulation of human microvascular tone in vivo and pave the way for further detailed investigation of the relative contribution of nNOS and eNOS in vascular regulation in human disease.
登录
查看更多内容
DOI：
10.1073/pnas.93.17.9142
发表时间：
1996-08-20
影响因子：
11.1
作者：
Chang, WJ;Iannaccone, ST;Stull, JT
通讯作者：
Stull, JT
DOI：
10.1152/ajpheart.00190.2007
发表时间：
2007-10-01
影响因子：
4.8
作者：
Bauser-Heaton, Holly D.;Bohlen, H. Glenn
通讯作者：
Bohlen, H. Glenn
DOI：
10.1124/jpet.105.094656
发表时间：
2006-02-01
影响因子：
3.5
作者：
Hatanaka, Y;Hobara, N;Kawasaki, H
通讯作者：
Kawasaki, H
影响因子：
6.3
作者：
PELLIGRINO, DA;KOENIG, HM;ALBRECHT, RF
通讯作者：
ALBRECHT, RF
影响因子：
64.8
作者：
PALMER, RMJ;ASHTON, DS;MONCADA, S
通讯作者：
MONCADA, S