Vascular effects of apelin in vivo in man
Vascular effects of apelin in vivo in man
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DOI：
10.1016/j.jacc.2008.06.013
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发表时间：
2008-09-09
影响因子：
24
通讯作者：
Newby, David E.
中科院分区：
文献类型：
--
作者：
Japp, Alan G.;Cruden, Nicholas L.;Newby, David E.
Apelin是G蛋白偶联受体（APJ）的内源性配体。这种新的途径在心血管系统中广泛表达，并且正在成为心血管稳态的重要介质。在临床前模型中，apelin引起静脉和动脉vasodilations.Methods血管apelin的影响进行了评估，在24名健康志愿者。在局部静脉输注（0.1至3 nmol/min）爱帕琳-36、（Pyr 1）爱帕琳-13和硝普钠（0.6 nmol/min）期间，通过Aellig技术测量手背静脉直径。在臂内输注apelin-36和（Pyr 1）apelin-13期间，通过静脉闭塞体积描记法测量前臂血流量（0.1至30 nmol/min），随后在存在或不存在“一氧化氮钳”的情况下，（一氧化氮合酶抑制剂，L-NG-单甲基精氨酸[8 μ mol/min]，与一氧化氮供体，硝普钠[90 - 900 ng/min]联合输注），结果虽然硝普钠引起静脉扩张（p < 0.0001），但apelin-36和（Pyr 1）apelin-13对手背静脉直径没有影响（p = 0.2）。两种爱帕琳同工型在前臂阻力血管中引起可再现的血管舒张（p < 0.0001）。（Pyr 1）apelin-13介导的血管舒张作用被一氧化氮钳夹减弱（p = 0.004），但不受阿司匹林影响（p = 0.7）。结论apelin对静脉张力无明显影响，但在人体内可引起一氧化氮依赖性动脉血管舒张。apelin-APJ系统值得进一步临床研究以确定其在心血管稳态中的作用。
Objectives This study was designed to establish the direct vascular effects of apelin in vivo in man.Background Apelin is the endogenous ligand for the previously orphaned G-protein-coupled receptor, APJ. This novel pathway is widely expressed in the cardiovascular system and is emerging as an important mediator of cardiovascular homeostasis. In pre-clinical models, apelin causes venous and arterial vasodilation.Methods Vascular effects of apelin were assessed in 24 healthy volunteers. Dorsal hand vein diameter was measured by the Aellig technique during local intravenous infusions (0.1 to 3 nmol/min) of apelin-36, (Pyr1) apelin-13, and sodium nitroprusside (0.6 nmol/min). Forearm blood flow was measured by venous occlusion plethysmography during intrabrachial infusions of apelin-36 and (Pyr1) apelin-13 (0.1 to 30 nmol/min) and subsequently in the presence or absence of a "nitric oxide clamp" (nitric oxide synthase inhibitor, L-NG-monomethylarginine [8 mu mol/min], coinfused with nitric oxide donor, sodium nitroprusside [90 to 900 ng/min]), or a single oral dose of aspirin (600 mg) or matched placebo.Results Although sodium nitroprusside caused venodilation (p < 0.0001), apelin-36 and (Pyr1) apelin-13 had no effect on dorsal hand vein diameter (p = 0.2). Both apelin isoforms caused reproducible vasodilation in forearm resistance vessels (p < 0.0001). (Pyr1) apelin-13-mediated vasodilation was attenuated by the nitric oxide clamp (p = 0.004) but unaffected by aspirin (p = 0.7).Conclusions Although having no apparent effect on venous tone, apelin causes nitric oxide-dependent arterial vasodilation in vivo in man. The apelin-APJ system merits further clinical investigation to determine its role in cardiovascular homeostasis.