Nazar M Shareef Mahmood, Almas Mr Mahmud, Ismail M Maulood
{"title":"褪黑激素对糖尿病大鼠主动脉血管内皮对血管紧张素 II 反应的影响","authors":"Nazar M Shareef Mahmood, Almas Mr Mahmud, Ismail M Maulood","doi":"10.1007/s10863-024-10032-z","DOIUrl":null,"url":null,"abstract":"<p><p>The current study explored melatonin (MEL) and its receptors, including MEL type 1 receptor (MT1) receptor and MEL type 2 receptor (MT2), along with the angiotensin-converting enzyme 2 (ACE<sub>2</sub>), influence on vascular responses to angiotensin II (Ang II) in rat aortic segments of normal and diabetic rats. The isolated aortic segments were exposed to MEL, the MEL agonist; ramelteon (RAM), the MEL antagonist; luzindole (LUZ), and an ACE<sub>2</sub> inhibitor (S, S)-2-(1-Carboxy-2-(3-(3,5-dichlorobenzyl)-3 H-imidazol-4-yl)-ethylamino)-4-methylpentanoic acid,) on Ang II-induced contractions in non-diabetic normal endothelium (non-DM E+), non-diabetic removed endothelium (non-DM E-), and streptozotocin-induced diabetic endothelium-intact (STZ-induced DM E+) rat aortic segments, as well as their combination in STZ-induced DM E + segments, were also included. The current results showed that MEL and RAM shifted Ang II dose-response curve (DRC) to the right side in non-DM E + and non-DM E- aorta but not in STZ-induced DM E + aorta. However, ACE<sub>2</sub> inhibition abolished Ang II degradation only in STZ-induced DM E + segments, not in non-DM E + segments. Additionally, the combinations of MEL-LUZ and RAM-ACE<sub>2</sub> inhibitor caused a rightward shift in Ang II response in STZ-induced DM E + segments, while the MEL-LUZ combination decreased Ang II DRC. The findings suggest that the effects of MEL and ACE<sub>2</sub> inhibitor on Ang II responses depend on the condition of the endothelium and the distribution of the MEL receptors.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The vascular influence of melatonin on endothelial response to angiotensin II in diabetic rat aorta.\",\"authors\":\"Nazar M Shareef Mahmood, Almas Mr Mahmud, Ismail M Maulood\",\"doi\":\"10.1007/s10863-024-10032-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The current study explored melatonin (MEL) and its receptors, including MEL type 1 receptor (MT1) receptor and MEL type 2 receptor (MT2), along with the angiotensin-converting enzyme 2 (ACE<sub>2</sub>), influence on vascular responses to angiotensin II (Ang II) in rat aortic segments of normal and diabetic rats. The isolated aortic segments were exposed to MEL, the MEL agonist; ramelteon (RAM), the MEL antagonist; luzindole (LUZ), and an ACE<sub>2</sub> inhibitor (S, S)-2-(1-Carboxy-2-(3-(3,5-dichlorobenzyl)-3 H-imidazol-4-yl)-ethylamino)-4-methylpentanoic acid,) on Ang II-induced contractions in non-diabetic normal endothelium (non-DM E+), non-diabetic removed endothelium (non-DM E-), and streptozotocin-induced diabetic endothelium-intact (STZ-induced DM E+) rat aortic segments, as well as their combination in STZ-induced DM E + segments, were also included. The current results showed that MEL and RAM shifted Ang II dose-response curve (DRC) to the right side in non-DM E + and non-DM E- aorta but not in STZ-induced DM E + aorta. However, ACE<sub>2</sub> inhibition abolished Ang II degradation only in STZ-induced DM E + segments, not in non-DM E + segments. Additionally, the combinations of MEL-LUZ and RAM-ACE<sub>2</sub> inhibitor caused a rightward shift in Ang II response in STZ-induced DM E + segments, while the MEL-LUZ combination decreased Ang II DRC. The findings suggest that the effects of MEL and ACE<sub>2</sub> inhibitor on Ang II responses depend on the condition of the endothelium and the distribution of the MEL receptors.</p>\",\"PeriodicalId\":2,\"journal\":{\"name\":\"ACS Applied Bio Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Bio Materials\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s10863-024-10032-z\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/31 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s10863-024-10032-z","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/31 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0
摘要
本研究探讨了褪黑激素(MEL)及其受体,包括MEL 1型受体(MT1)和MEL 2型受体(MT2),以及血管紧张素转换酶2(ACE2)对正常大鼠和糖尿病大鼠主动脉瓣血管对血管紧张素II(Ang II)反应的影响。将离体大鼠主动脉片段暴露于 MEL(MEL 激动剂)、ramelteon(RAM)(MEL 拮抗剂)、luzindole(LUZ)、luzindole(LUZ)、luzindole(LUZ)、luzindole对非糖尿病正常内皮(非糖尿病 E+)的 Ang II 诱导的收缩有影响的药物有:卢吲哚(LUZ)和 ACE2 抑制剂(S, S)-2-(1-羧基-2-(3-(3,5-二氯苄基)-3 H-咪唑-4-基)-乙基氨基)-4-甲基戊酸、)研究还包括非糖尿病去内皮(非 DM E-)和链脲佐菌素诱导的糖尿病内皮-非内皮(STZ-诱导的 DM E+)大鼠主动脉节段以及它们在 STZ-诱导的 DM E + 节段中的组合。目前的研究结果表明,MEL和RAM能使非DM E+和非DM E-大鼠主动脉中的Ang II剂量反应曲线(DRC)向右侧移动,但不能使STZ诱导的DM E+大鼠主动脉中的DRC向右侧移动。然而,ACE2抑制仅在STZ诱导的DM E +节段中抑制了Ang II降解,而在非DM E +节段中没有抑制。此外,MEL-LUZ 和 RAM-ACE2 抑制剂的组合会导致 STZ 诱导的 DM E + 节段的 Ang II 反应右移,而 MEL-LUZ 组合则会降低 Ang II DRC。研究结果表明,MEL 和 ACE2 抑制剂对 Ang II 反应的影响取决于内皮的状况和 MEL 受体的分布。
The vascular influence of melatonin on endothelial response to angiotensin II in diabetic rat aorta.
The current study explored melatonin (MEL) and its receptors, including MEL type 1 receptor (MT1) receptor and MEL type 2 receptor (MT2), along with the angiotensin-converting enzyme 2 (ACE2), influence on vascular responses to angiotensin II (Ang II) in rat aortic segments of normal and diabetic rats. The isolated aortic segments were exposed to MEL, the MEL agonist; ramelteon (RAM), the MEL antagonist; luzindole (LUZ), and an ACE2 inhibitor (S, S)-2-(1-Carboxy-2-(3-(3,5-dichlorobenzyl)-3 H-imidazol-4-yl)-ethylamino)-4-methylpentanoic acid,) on Ang II-induced contractions in non-diabetic normal endothelium (non-DM E+), non-diabetic removed endothelium (non-DM E-), and streptozotocin-induced diabetic endothelium-intact (STZ-induced DM E+) rat aortic segments, as well as their combination in STZ-induced DM E + segments, were also included. The current results showed that MEL and RAM shifted Ang II dose-response curve (DRC) to the right side in non-DM E + and non-DM E- aorta but not in STZ-induced DM E + aorta. However, ACE2 inhibition abolished Ang II degradation only in STZ-induced DM E + segments, not in non-DM E + segments. Additionally, the combinations of MEL-LUZ and RAM-ACE2 inhibitor caused a rightward shift in Ang II response in STZ-induced DM E + segments, while the MEL-LUZ combination decreased Ang II DRC. The findings suggest that the effects of MEL and ACE2 inhibitor on Ang II responses depend on the condition of the endothelium and the distribution of the MEL receptors.