Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Eur J Pharmacol. 2020 Sep 5;882:173278. doi: 10.1016/j.ejphar.2020.173278. Epub 2020 Jun 13.
Metabolic syndrome (MetS) is a common disorder that is associated with hypertension and poses a significant cardiovascular risk. Deactivation of extra-neuronal norepinephrine is mediated by catechol-O-methyltransferase (COMT). Endogenous 2-methoxyestradiol (2ME) is a product of COMT activity. The current study investigated the impact of 2ME on MetS-induced hypertension and the possible alterations in COMT expression and activity in rats. Animals were randomly divided into 4 groups. Group 1 received drinking water and standard food pellets. Groups 2, 3 and 4 were subjected to experimental induction of MetS. Animals in groups 3 and 4 were given daily IP injection of 2ME (25 and 50 mg/kg, respectively). MetS animals showed significant increases in body weight gain and visceral fat, fasting blood glucose and serum insulin and insulin resistance. Meanwhile, MetS was associated with a significant hypertriglyceridemia. Further, MetS significantly increased systolic, diastolic and mean arterial blood pressure. These effects were associated with significant reduction in COMT expression in the liver, kidneys and aorta as well as reduced hepatic activity. 2ME inhibited the alterations in body weight gain, visceral fat accumulation, fasting blood glucose and serum insulin, insulin resistance and serum triglycerides. Elevations in blood pressure were significantly inhibited by 2ME. Also, it attenuated the decrease in liver, kidney and aorta COMT expression and hepatic COMT activity. MetS was associated with elevated epinephrine and norepinephrine levels. Only the higher dose of 2ME significantly mitigated the rise in epinephrine level. In conclusion, 2ME protects against MetS-induced hypertension and averts COMT inhibited expression and activity.
代谢综合征（MetS）是一种常见的疾病，与高血压有关，并且存在重大的心血管风险。去甲肾上腺素的神经元外失活是由儿茶酚-O-甲基转移酶（COMT）介导的。内源性 2-甲氧基雌二醇（2ME）是 COMT 活性的产物。本研究探讨了 2ME 对 MetS 诱导的高血压的影响，以及 COMT 表达和活性在大鼠中的可能改变。动物被随机分为 4 组。第 1 组给予饮用水和标准食物颗粒。第 2、3 和 4 组接受 MetS 的实验诱导。第 3 和 4 组动物每天给予腹腔注射 2ME（分别为 25 和 50mg/kg）。MetS 动物的体重增加和内脏脂肪、空腹血糖和血清胰岛素以及胰岛素抵抗显著增加。同时，MetS 与显著的高甘油三酯血症有关。此外，MetS 显著增加收缩压、舒张压和平均动脉压。这些作用与肝脏、肾脏和主动脉中 COMT 表达的显著减少以及肝活性的降低有关。2ME 抑制体重增加、内脏脂肪堆积、空腹血糖和血清胰岛素、胰岛素抵抗和血清甘油三酯的改变。2ME 显著抑制血压升高。此外，它还减轻了肝脏、肾脏和主动脉中 COMT 表达和肝 COMT 活性的降低。MetS 与肾上腺素和去甲肾上腺素水平升高有关。只有较高剂量的 2ME 显著减轻了肾上腺素水平的升高。总之，2ME 可预防 MetS 诱导的高血压，并防止 COMT 抑制表达和活性。
