Differential effects of endothelin receptor activation on cyclic flow variations in rat mesenteric arteries.
Differential effects of endothelin receptor activation on cyclic flow variations in rat mesenteric arteries.
复制标题
内皮素受体激活对大鼠肠系膜动脉循环血流变化的不同影响。
DOI：
10.1161/01.cir.96.10.3641
复制
发表时间：
1997
期刊：
影响因子：
37.8
通讯作者：
Willerson,JT
中科院分区：
文献类型：
--
作者：
Fujise,K;Stacy,L;Beck,P;Yeh,ET;Chuang,A;Brock,TA;Willerson,JT
循环性血流变异（cyclic flow variations，CFVs）是指血小板粘附-聚集和血管收缩的重复循环，随后血小板血栓脱落并恢复血管损伤部位的血流。虽然内皮素A（ETA）和内皮素B（ET B）受体的激活导致血管收缩和一氧化氮释放，分别内源性内皮素-1（ET-1）及其受体在CFVs.Methods和ResultsA侧分支的雄性Wistar大鼠肠系膜动脉插管和一个短段的动脉机械损伤诱导CFVs的作用。盐水输注20分钟后，将盐水（阴性对照）、BQ-123（ETA受体拮抗剂，10 μg/min）、BQ-788（ETB受体拮抗剂，10 μg/min）或sarafotoxin S6 c（ETB受体激动剂，10 ng/min）从侧分支输注到损伤的动脉段中20分钟。观察管腔狭窄百分比（%）以及近端和远端血管直径，并使用活体视频显微镜和微米校准的视频屏幕每分钟定量测量。BQ-123和萨拉福毒素S6 c均显著降低了由平均管腔狭窄表示的CFV（与盐水相比，BQ-123和萨拉福毒素S6 c分别降低了29±13%和27±11%;两者P<0.05）。相比之下，BQ-788显著增加CFV（与盐水相比增加33±6%，P<0.05）。此外，在动脉灌流液中加入N ω-硝基-L-精氨酸甲酯（L-NAME，一种一氧化氮合酶抑制剂，10 - 5 mol/L）后，萨拉福毒素S6 c对CFV的抑制作用完全消失（与加入L-NAME的生理盐水相比，增加16.1±5%，P=NS）。此外，BQ-123引起损伤段远端血管直径的显著增加（增加12±4%，与生理盐水相比P<0.05）。ETA和ETB受体在CFV中具有不同的作用：ETA受体拮抗和ETB受体刺激降低CFV，后者至少部分地通过增加一氧化氮形成。
BackgroundCyclic flow variations (CFVs) represent repetitive cycles of platelet adherence–aggregation and vasoconstriction, followed by dislodgment of platelet thrombi and restoration of blood flow at the site of vascular injury. Although activation of endothelin A (ETA) and endothelin B (ETB) receptors leads to vasoconstriction and nitric oxide release, respectively, the roles of endogenous endothelin-1 (ET-1) and its receptors in CFVs are unknown.Methods and ResultsA side branch of a mesenteric artery of male Wistar rats was cannulated and a short segment of the artery was mechanically injured to induce CFVs. After 20 minutes of saline infusion, either saline (negative control), BQ-123 (ETA receptor antagonist, 10 μg/min), BQ-788 (ETB receptor antagonist, 10 μg/min), or sarafotoxin S6c (ETB receptor agonist, 10 ng/min) was infused for 20 minutes from the side branch into the injured arterial segment. Percent (%) luminal stenosis as well as proximal and distal vessel diameters were observed and quantitatively measured every minute using intravital video microscopy and a micrometer-calibrated video screen. Both BQ-123 and sarafotoxin S6c significantly reduced CFVs represented by the mean luminal stenosis (BQ-123=29±13% and sarafotoxin S6c=27±11% reduction, respectively;P<.05 for both, compared with saline). In contrast, BQ-788 significantly increased CFVs (33±6% increase,P<.05 compared with saline). Moreover, the inhibitory effect of sarafotoxin S6c on CFVs was completely abolished in the presence ofNω-nitro-l-arginine methyl ester (L-NAME) (a nitric oxide synthase inhibitor, 10−5mol/L) in superfusate over the arteries (16.1±5% increase,P=NS compared with saline in the presence of L-NAME). In addition, BQ-123 caused a significant increase in the diameter of the vessel distal to the injured segment (12±4% increase,P<.05 compared with saline).ConclusionsEndogenous ET-1 release from sites of vascular injury contributes to CFVs and vasomotor tone in the rat mesenteric artery CFV model. ETA and ETB receptors have differential roles in CFVs: ETA receptor antagonism and ETB receptor stimulation reduce CFVs, the latter at least partially through increased nitric oxide formation.