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大鼠对侧颈动脉球囊损伤后内皮素收缩性高反应性：ET 受体和超氧阴离子的综合作用。

Endothelinergic Contractile Hyperreactivity in Rat Contralateral Carotid to Balloon Injury: Integrated Role for ET Receptors and Superoxide Anion.

机构信息

Department of Biosciences Applied to Pharmacy, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.

Department of Pharmacology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, SP, Brazil.

出版信息

Biomed Res Int. 2017;2017:3137580. doi: 10.1155/2017/3137580. Epub 2017 Sep 14.

DOI:10.1155/2017/3137580
PMID:29062837
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5618786/
Abstract

Temporal consequences of neurocompensation to balloon injury on endothelinergic functionality in rat contralateral carotid were evaluated. Rats underwent balloon injury in left carotid and were treated with CP-96345 (NK antagonist). Concentration-response curves for endothelin-1 were obtained in contralateral (right) carotid at 2, 8, 16, 30, or 45 days after surgery in the absence or presence of BQ-123 (ET antagonist), BQ-788 (ET antagonist), or Tempol (superoxide-dismutase mimic). Endothelin-1-induced calcium mobilization was evaluated in functional assays carried out with BQ-123, BQ-788, or Tempol. Endothelin-1-induced NADPH oxidase-driven superoxide generation was measured by lucigenin chemiluminescence assays performed with BQ-123 or BQ-788. Endothelin-1-induced contraction was increased in contralateral carotid from the sixteenth day after surgery. This response was restored in CP-96345-treated rats. Endothelium removal or BQ-123 did not change endothelin-1-induced contraction in contralateral carotid. This response was restored by BQ-788 or Tempol. Contralateral carotid exhibited an increased endothelin-1-induced calcium mobilization, which was restored by BQ-788 or Tempol. Contralateral carotid exhibited an increased endothelin-1-induced lucigenin chemiluminescence, which was restored by BQ-788. We conclude that the NK-mediated neurocompensatory response to balloon injury elicits a contractile hyperreactivity to endothelin-1 in rat contralateral carotid by enhancing the muscular ET-mediated NADPH oxidase-driven generation of superoxide, which activates calcium channels.

摘要

评价了神经补偿对球囊损伤后大鼠对侧颈内动脉内皮素功能的时间后果。 大鼠进行了左颈动脉球囊损伤，并接受 CP-96345（NK 拮抗剂）治疗。 在手术后第 2、8、16、30 或 45 天，在不存在或存在 BQ-123（ET 拮抗剂）、BQ-788（ET 拮抗剂）或 Tempol（超氧化物歧化酶模拟物）的情况下，获得了对侧（右）颈动脉中内皮素-1 的浓度-反应曲线。 在存在 BQ-123、BQ-788 或 Tempol 的功能测定中评估了内皮素-1 诱导的钙动员。 通过使用 BQ-123 或 BQ-788 进行的 lucigenin 化学发光测定测量了内皮素-1 诱导的 NADPH 氧化酶驱动的超氧化物生成。 内皮素-1 诱导的收缩在手术后第 16 天增加。 这种反应在 CP-96345 处理的大鼠中得到恢复。 内皮去除或 BQ-123 未改变对侧颈动脉中内皮素-1 诱导的收缩。 这种反应由 BQ-788 或 Tempol 恢复。 对侧颈内动脉表现出增加的内皮素-1 诱导的钙动员，这由 BQ-788 或 Tempol 恢复。 对侧颈内动脉表现出增加的内皮素-1 诱导的 lucigenin 化学发光，这由 BQ-788 恢复。 我们得出结论，NK 介导的对球囊损伤的神经补偿反应通过增强肌肉 ET 介导的 NADPH 氧化酶驱动的超氧化物产生，从而激活钙通道，引起大鼠对侧颈动脉内皮素-1 的收缩性高反应性。

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本文引用的文献

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Impairment of α1-adrenoceptor-mediated calcium influx in contralateral carotids following balloon injury: beneficial effect of superoxide anions.球囊损伤后对侧颈动脉α1-肾上腺素能受体介导的钙内流受损：超氧阴离子的有益作用。
Eur J Pharmacol. 2014 Jan 15;723:397-404. doi: 10.1016/j.ejphar.2013.10.066. Epub 2013 Nov 8.
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Pathophysiology of vascular remodeling in hypertension.高血压血管重塑的病理生理学
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Cross-talk with β2 -adrenoceptors enhances ligand affinity properties from endothelial alpha1 D -adrenoceptors that mediates carotid relaxation.β2-肾上腺素能受体的相互作用增强了介导颈动脉松弛的内皮细胞α1D-肾上腺素能受体的配体亲和力特性。
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