P2u receptor-mediated release of endothelium-derived relaxing factor nitric oxide and endothelium-derived hyperpolarizing factor from cerebrovascular endothelium in rats

P2u receptor-mediated release of endothelium-derived relaxing factor nitric oxide and endothelium-derived hyperpolarizing factor from cerebrovascular endothelium in rats
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DOI:
10.1161/01.str.30.5.1125
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发表时间:
1999-05-01
期刊:
影响因子:
8.3
通讯作者:
Bryan, RM
Bryan, RM
中科院分区:
医学1区
文献类型:
--
作者:
You, JP;Johnson, TD;Bryan, RM

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背景与目的:UTP刺激内皮上的P-2U嘌呤受体,通过释放内皮源性松弛因子/一氧化氮(EDRF/NO)和一种未知的松弛因子来扩张大鼠大脑中动脉(MCA),本研究的目的是确定这种未知的松弛因子是否是内皮源性超极化因子(EDHF)。结果:在一项研究中,MCAS的静息外径为209±7微米(n=10)。给予UTP后,MCAS呈浓度依赖性扩张。用N-G-硝基-L-精氨酸甲酯(L-NAME)(1mU/L至1 mmoL/L)抑制NO合成酶并不降低UTP的最大反应,但确实使量效曲线右移,用血红蛋白(1或10mU/L)清除NO,或用ODQ(1或10mU/L)抑制鸟苷环化酶对UTP介导的扩张的影响与L-NAME相似。在L-NAME存在下,10MU/L UTP引起的血管扩张伴随有13+/-2 mV(P
Background and Purpose-Stimulation of P-2u purinoceptors by UTP on endothelium dilates the rat middle cerebral artery (MCA) through the release of endothelium-derived relaxing factor/nitric oxide (EDRF/NO) and an unknown relaxing factor, The purpose of this study was to determine whether this unknown relaxing factor is endothelium-derived hyperpolarizing factor (EDHF).Methods-Rat MCAs were isolated, cannulated, pressurized, and luminally perfused. UTP was added to the luminal perfusate to elicit dilations.Results-Resting outside diameter of the MCAs in one study was 209+/-7 mu m (n = 10). The MCAs showed concentration dependent dilations with UTP administration. Inhibition of NO synthase with N-G-nitro-L-arginine methyl ester (L-NAME) (1 mu mol/L to 1 mmol/L) did not diminish the maximum response to UTP but did shift the concentration-response curve to the right, Scavenging NO with hemoglobin (1 or 10 mu mol/L) or inhibition of guanylate cyclase with ODQ (1 or 10 mu mol/L) had effects on the UTP-mediated dilations similar to those of L-NAME. In the presence of L-NAME, dilations induced by 10 mu mol/L UTP were accompanied by 13+/-2 mV (P