Reduced Relaxant Response to Adenine in the Superior Mesenteric Artery of Spontaneously Hypertensive Rats

Reduced Relaxant Response to Adenine in the Superior Mesenteric Artery of Spontaneously Hypertensive Rats
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DOI:
10.1248/bpb.b21-00437
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发表时间:
2021-10-01
影响因子:
2
通讯作者:
Kobayashi, Tsuneo
Kobayashi, Tsuneo
中科院分区:
医学4区
文献类型:
--
作者:
Matsumoto, Takayuki;Takayanagi, Keisuke;Kobayashi, Tsuneo

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我们使用新鲜分离的自发性高血压大鼠(SHR)及其对照组Wistar京都(WKY)大鼠的上级肠系膜动脉研究了对核碱基腺嘌呤的血管反应。在器官浴中的分离节段中评估了内皮依赖性和内皮非依赖性舒张作用。还检测到血栓素A(2)和前列腺素I-2代谢产物的释放。腺嘌呤以浓度依赖性方式诱导内皮完整和内皮剥脱动脉的血管舒张。在SHR组中,腺嘌呤诱导的舒张作用在内皮完整的环中与WKY组相比轻微但显著减少。然而,两组之间内皮剥脱环的舒张相似。腺嘌呤介导的舒张在SHR和WKY组之间的上级肠系膜动脉的差异被消除内皮剥脱和一氧化氮(NO)合酶抑制剂。在腺嘌呤存在和不存在的情况下,与WKY相比,SHR倾向于具有更高水平的血栓素A(2)和前列腺素I-2代谢物。然而,腺嘌呤并没有诱导这些物质在SHR和WKY组的动脉中的释放。这些结果表明,减少腺嘌呤介导的舒张上级肠系膜动脉在SHR是由于缺乏来自内皮源性NO的贡献,而不是从释放前列腺素。
We investigated the vascular response to nucleobase adenine using freshly isolated superior mesenteric arteries of spontaneously hypertensive rats (SHR) and its control, Wistar Kyoto (WKY) rats. Endothelium-dependent and endothelium-independent relaxations were assessed in isolated segments in an organ bath. The releases of the metabolites of thromboxane A(2) and prostaglandin I-2 were also detected. Adenine induced vasorelaxation in both the endothelium-intact and endothelium-denuded arteries in a concentration-dependent manner. In the SHR group, the adenine-induced relaxation was slightly but significantly reduced in the endothelium-intact rings when compared with that in the WKY group. However, the relaxation in the endothelium-denuded rings were similar between the two groups. The difference in the adenine-mediated relaxation in the superior mesenteric arteries between the SHR and WKY groups was eliminated by endothelial denudation and a nitric oxide (NO) synthase inhibitor. In the absence and presence of adenine, SHR tended to have higher levels of metabolites of thromboxane A(2) and prostaglandin I-2 compared with WKY. However, adenine did not induce the release of these substances in the arteries in both the SHR and WKY groups. These results suggest that the reduced adenine-mediated relaxation in the superior mesenteric arteries in SHR is due to a lack of contribution from the endothelium-derived NO and not from the release of prostanoids.