首页> 美国卫生研究院文献>British Journal of Pharmacology and Chemotherapy >Comparison of the contractile and calcium-increasing properties of platelet-activating factor and endothelin-1 in the rat mesenteric artery and vein
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Comparison of the contractile and calcium-increasing properties of platelet-activating factor and endothelin-1 in the rat mesenteric artery and vein

机译:大鼠肠系膜动脉和静脉中血小板活化因子和内皮素-1的收缩和增钙特性的比较

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摘要

class="enumerated" style="list-style-type:decimal">In the present study, the properties of endothelin-1 (ET-1) and platelet-activating factor (PAF) in inducing contraction and increased intracellular-free calcium level in rat mesenteric arteries and veins were studied. Furthermore, measurements of cytosolic ([Ca]c) and nuclear ([Ca]n) Ca2+ were performed by confocal microscopy.PAF, at a concentration of 1 μM, and the selective ETB agonists, IRL-1620 and sarafotoxin S6C (100 nM), induced a marked constriction and increase in [Ca]i in the mesenteric vein but not in the artery. On the other hand, endothelin-1 (1–100 nM) induced a significant concentration-dependent nifedipine-insensitive increase in tension and [Ca]i in both arteries and veins.Those responses to endothelin-1 were significantly reduced by the ETA receptor antagonist, BQ-123 (10−6 M), on both types of vessels, whereas the selective ETB receptor antagonist, BQ-788, inhibited only the venous responses. The mixed ETA/ETB receptor antagonist, SB 209670, reduced the ET-1-induced venous responses to the same level of that found in presence of BQ-123 or BQ-788. However, concomitant applications of BQ-123 and BQ-788 reduced the vasoconstriction below to that induced by ETA or ETB blockade without further affecting [Ca]i.PAF and the selective ETB agonists IRL-1620, induced a sustained increase of [Ca]c and [Ca]n solely in venous cells and ET-1 in both arterial and venous smooth muscle cells.Thus, PAF increases total intracellular calcium concentration and tension on the smooth muscle cells from venous origin only. Furthermore, ET-1-induced vasoactive as well as [Ca]i and [Ca]n increasing effects are mediated by distinct receptors on venous and arterial smooth muscles.
机译:class =“ enumerated” style =“ list-style-type:decimal”> <!-list-behavior =枚举前缀-word = mark-type = decimal max-label-size = 0-> 在本研究中,研究了内皮素-1(ET-1)和血小板活化因子(PAF)在大鼠肠系膜动脉和静脉中诱导收缩和增加细胞内游离钙水平的特性。此外,通过共聚焦显微镜对胞浆(CaCa)和核Ca(sCa)2+进行测量。 PAF,浓度为1μM ,选择性ETB激动剂IRL-1620和sarafotoxin S6C(100 nM)引起肠系膜静脉而非动脉中的显着收缩和[Ca] i升高。另一方面,内皮素-1(1–100 nM)引起浓度和硝苯地平不敏感的浓度依赖性动脉和静脉紧张性和[Ca] i升高。 对内皮素-1的反应在两种类型的血管上,ETA受体拮抗剂BQ-123(10 −6 M)均可显着降低血管紧张素转换酶,而选择性ETB受体拮抗剂BQ-788仅抑制静脉反应。混合的ETA / ETB受体拮抗剂SB 209670将ET-1诱导的静脉反应降低到与BQ-123或BQ-788存在时相同的水平。但是,BQ-123和BQ-788的同时使用将血管收缩降低到了ETA或ETB阻断诱导的水平,而没有进一步影响[Ca] i。 PAF和选择性ETB激动剂IRL-1620仅在静脉细胞中[Ca] c和[Ca] n持续增加,在动脉和静脉平滑肌细胞中ET-1持续升高。 因此,PAF会增加细胞内总钙离子浓度和平滑度仅来自静脉的肌肉细胞。此外,ET-1诱导的血管活性以及[Ca] i和[Ca] n 的增加作用是由静脉和动脉平滑肌上不同的受体介导的。

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