Nitric oxide, prostanoid and non-NO, non-prostanoid involvement in acetylcholine relaxation of isolated human small arteries
Nitric oxide, prostanoid and non-NO, non-prostanoid involvement in acetylcholine relaxation of isolated human small arteries
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DOI：
10.1038/sj.bjp.0703041
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发表时间：
2000-01-01
影响因子：
7.3
通讯作者：
Mulvaney, NJ
中科院分区：
文献类型：
--
作者：
Buus, NH;Simonsen, U;Mulvaney, NJ
1本研究的主要目的是探讨一氧化氮（NO）在乙酰胆碱（ACh）舒张人皮下小动脉中的作用。2用肌电描记仪记录动脉等长收缩张力、NO浓度和平滑肌膜电位。NO合成酶抑制剂N-G-硝基-L-精氨酸（L-NOARG）对ACh的浓度-反应曲线有轻微的显著影响，在L-NOARG存在下，吲哚美辛仅引起ACh舒张的轻微额外的α位移。4 NO清除剂氧合血红蛋白减弱ACh和NO供体S-亚硝基-N-乙酰青霉胺（SNAP）的舒张。用H-1-[1，2，4]恶二唑并[4，3a]喹喔啉-1-酮（ODQ）抑制鸟苷酸环化酶，用β-乙烯基-1，N2-乙烯基-8-溴代鸟苷-3 '，5'-环硫代磷酸酯（Rp-异构体）抑制蛋白激酶G，可轻微减弱ACh舒张，但可消除SNAP诱导的舒张。5 ACh诱导舒张，但不增加游离NO浓度。相比之下，对于相等的松弛，SNAP增加NO浓度32+/-8 nM.6 ACh超极化动脉平滑肌细胞11.4+/-1.3 mV和10.5 +/-1.3 mV的L-NOARG的情况下，分别。SNAP仅引起1.6 +/- 0.9 mV的超极化。7在吲哚美辛和L-NOARG存在下，ACh松弛几乎不受去甲二氢愈创木酸脂氧合酶抑制或17-十八炔酸或益康唑细胞色素P450抑制的影响。ACh松弛被Charybdotoxin和apamin的组合强烈地降低，但是细胞外钾浓度的小增量不诱导松弛。8该研究表明，NO/L-精氨酸途径存在于人类皮下小动脉中，并且在有限程度上参与ACh诱导的松弛。该研究还表明花生四烯酸代谢产物的贡献很小。然而，ACh舒张主要依赖于非NO、非前列腺素类内皮依赖性超极化。
1 The main purpose of the study was Co clarify to which extent nitric oxide (NO) contributes to acetylcholine (ACh) induced relaxation of human subcutaneous small arteries.2 Arterial segments were mounted in myographs for recording of isometric tension, NO concentration and smooth muscle membrane potential.3 In noradrenaline-contracted arteries, ACh induced endothelium-dependent relaxations. The NO synthase inhibitor, N-G-nitro-L-arginine (L-NOARG) had a small significant effect on the concentration-response curves for ACh, and in the presence of L-NOARG indomethacin only caused a small additional rightward shift in the ACh relaxation.4 The NO scavenger, oxyhaemoglobin attenuated relaxations for ACh and for the NO donor S-nitroso-N-acetylpenicillamine (SNAP). Inhibition of guanylyl cyclase with H-1-[1,2,4]oxadiazolo[4,3a]quinoxaline-1-one (ODQ), and inhibition of protein kinase G with beta-Ethenyl-1, N2-etheno-8-bromoguanosine- 3', 5'- cyclic monophosphorothioate, Rp-isomer, slightly attenuated ACh relaxation, but abolished SNAP induced relaxation.5 ACh induced relaxation without increases in the free NO concentration. In contrast, for equivalent relaxation, SNAP increased the NO concentration 32+/-8 nM.6 ACh hyperpolarized the arterial smooth muscle cells with 11.4+/-1.3 mV and 10.5 +/- 1.3 mV in the absence and presence of L-NOARG, respectively. SNAP only elicited a hyperpolarization of 1.6 +/- 0.9 mV.7 In the presence of indomethacin and L-NOARG, ACh relaxation was almost unaffected by lipoxygenase inhibition with nordihydroguaiaretic acid, or cytochrome P450 inhibition with 17-octadecynoic acid or econazole. ACh relaxation was strongly reduced by the combination of charybdotoxin and apamin, but small increments in the extracellular potassium concentration induced no relaxations.8 The study demonstrates that the NO/L-arginine pathway is present in human subcutaneous small arteries and to a limited extent is involved in ACh induced relaxation. The study also suggests a small contribution of arachidonic acid metabolites. However, ACh relaxation is mainly dependent on a non-NO, non-prostanoid endothelium dependent hyperpolarization.