Department of Internal Medicine and Geriatrics, Zhongnan Hospital, Wuhan University School of Medicine, Wuhan, 430071, China.
Department of Physiology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
Eur J Pharmacol. 2021 Jun 15;901:174070. doi: 10.1016/j.ejphar.2021.174070. Epub 2021 Mar 31.
The aim of this study was to investigate the reaction of pancreatic and mesenteric artery to 5-hydroxytryptamine (5-HT, serotonin) and the mechanism of nitric oxide in diabetes. Diabetic mice were induced by streptozotocin through intraperitoneal injection. The vascular tension of the pancreatic, mesenteric and brain basilar arteries in diabetic and control mice were measured by myograph in the applications of angiotensin II, 5-HT, 5-HT receptor agonist 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI), 5-HT receptor agonist sumatriptan, 5-HT receptor agonist BW723C86, 5-HT receptor antagonist Palonosetron and 5-HT receptor antagonist Sarpogrelate. The effect of 5-HT on arteries pretreated with L-NAME and sodium nitroprusside (SNP) on arteries pretreated with norepinephrine were measured. The mRNA expressions of eNOS, 5-HT, 5-HT, 5-HT and 5-HT in pancreatic and mesenteric arteries were measured by Real-time PCR. The concentration of 5-HT in plasma and eNOS in pancreatic and mesenteric arteries were tested. Our results showed that the tension of pancreatic and mesenteric arteries in diabetic mice impaired to 5-HT, but not Ang II, and to DOI and sumatriptan, but normalized by incubation with L-NAME. Pancreatic and mesenteric arteries showed no differences to SNP after pretreated with NE between diabetic and control mice. The mRNA of eNOS and 5-HT receptors in pancreatic and mesenteric artery showed no difference between control and diabetic mice. We conclude that the effect of 5-HT on the tension of pancreatic and mesenteric arteries decrease in diabetic mice. It may due to the decreased activity of 5-HT receptors and the activation of eNOS, which causes nitric oxide to release more and makes the tension of vessels decreased.
本研究旨在探讨 5-羟色胺（5-HT，血清素）对胰腺和肠系膜动脉的反应以及一氧化氮在糖尿病中的作用机制。通过腹腔注射链脲佐菌素诱导糖尿病小鼠。应用血管紧张素 II、5-HT、5-HT 受体激动剂 2,5-二甲氧基-4-碘苯丙胺盐酸盐（DOI）、5-HT 受体激动剂舒马曲坦、5-HT 受体激动剂 BW723C86、5-HT 受体拮抗剂帕洛诺司琼和 5-HT 受体拮抗剂沙格雷酯，测量糖尿病和对照组小鼠胰腺、肠系膜和基底脑动脉的血管张力。测量预先用 L-NAME 和硝普钠（SNP）处理的 5-HT 对预先用去甲肾上腺素处理的动脉的影响。通过实时 PCR 测量胰腺和肠系膜动脉中 eNOS、5-HT、5-HT、5-HT 和 5-HT 的 mRNA 表达。检测血浆中 5-HT 浓度和胰腺和肠系膜动脉中 eNOS 的浓度。结果显示，糖尿病小鼠的胰腺和肠系膜动脉对 5-HT 的张力受损，但对 Ang II 无影响，对 DOI 和舒马曲坦的反应正常，但用 L-NAME 孵育后可恢复正常。糖尿病和对照组小鼠的胰腺和肠系膜动脉在预先用去甲肾上腺素处理后对 SNP 无差异。胰腺和肠系膜动脉中 eNOS 和 5-HT 受体的 mRNA 在对照组和糖尿病组小鼠之间无差异。我们得出结论，糖尿病小鼠 5-HT 对胰腺和肠系膜动脉张力的影响降低。这可能是由于 5-HT 受体活性降低和 eNOS 激活，导致一氧化氮释放增加，血管张力降低。
