Department of Cardiovascular Medicine, The Second Affiliated Hospital of Chengdu Medical College, Chengdu, 610000 Sichuan, China.
Department of Geriatrics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, 610000 Sichuan, China.
Oxid Med Cell Longev. 2023 Feb 21;2023:5352959. doi: 10.1155/2023/5352959. eCollection 2023.
-Opioid receptors (-OR) are widely used to regulate the activity of the cardiovascular system. To explore the effect and mechanism of -OR on salt-sensitive hypertensive endothelial dysfunction, we used Dah1 rats to construct a rat model of salt-sensitive hypertension on a high-salt (HS) diet. Then, the rats were treated with -OR activators U50,488H (1.25 mg/kg) and inhibitor nor-BNI (2.0 mg/kg) for 4 weeks, respectively. The rat aortas were collected to detect the contents of NO, ET-1, AngII, NOS, T-AOC, SO, and NT. Protein expression was determined for NOS, Akt, and Caveolin-1. In addition, the vascular endothelial cells were extracted, and the levels of NO, TNF-, IL-1, IL-6, IL-8, IL-10, p-Akt, and p-eNOS in cell supernatants were detected. In vivo results showed that compared with the HS group, treated with U50,488H promoted rats' vasodilation by increasing the NO content and decreasing ET-1 and AngII contents. U50,488H reduced endothelial cell apoptosis and attenuated vascular, smooth muscle cell and endothelial cell injury. U50,488H also enhanced the rats' response to oxidative stress by increasing the NOS and T-AOC contents. Moreover, U50,488H increased the eNOS, p-eNOS, Akt, and p-AKT expression and decreased the iNOS and Caveolin-1 expression. In vitro results showed that U50,488H promoted NO, IL-10, p-Akt, and p-eNOS levels in endothelial cell supernatants versus the HS group. And U50,488H reduced the adhesion of peripheral blood mononuclear cells and polymorphonuclear neutrophils to endothelial cells and the migration function of polymorphonuclear neutrophils. Our study suggested that -OR activation may improve vascular endothelial dysfunction in salt-sensitive hypertensive rats through the PI3K/Akt/eNOS signaling pathway. This may be a potential therapeutic approach in the treatment of hypertension.
阿片受体（-OR）广泛用于调节心血管系统的活动。为了探讨 -OR 对盐敏感型高血压内皮功能障碍的作用和机制，我们使用 Dah1 大鼠在高盐（HS）饮食上构建了盐敏感型高血压大鼠模型。然后，分别用 -OR 激动剂 U50,488H（1.25mg/kg）和抑制剂 nor-BNI（2.0mg/kg）处理大鼠 4 周。收集大鼠主动脉以检测 NO、ET-1、AngII、NOS、T-AOC、SO 和 NT 的含量。测定 NOS、Akt 和 Caveolin-1 的蛋白表达。此外，提取血管内皮细胞，检测细胞上清液中 NO、TNF-、IL-1、IL-6、IL-8、IL-10、p-Akt 和 p-eNOS 的水平。体内结果表明，与 HS 组相比，用 U50,488H 处理促进了大鼠的血管舒张，增加了 NO 的含量，降低了 ET-1 和 AngII 的含量。U50,488H 减少了内皮细胞凋亡，减轻了血管、平滑肌细胞和内皮细胞损伤。U50,488H 还通过增加 NOS 和 T-AOC 的含量增强了大鼠对氧化应激的反应。此外，U50,488H 增加了 eNOS、p-eNOS、Akt 和 p-AKT 的表达，降低了 iNOS 和 Caveolin-1 的表达。体外结果表明，与 HS 组相比，U50,488H 促进了内皮细胞上清液中 NO、IL-10、p-Akt 和 p-eNOS 的水平。并且 U50,488H 减少了外周血单核细胞和多形核白细胞与内皮细胞的黏附以及多形核白细胞的迁移功能。我们的研究表明，-OR 激活可能通过 PI3K/Akt/eNOS 信号通路改善盐敏感型高血压大鼠的血管内皮功能障碍。这可能是治疗高血压的一种潜在治疗方法。
