Department of Pharmacology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Eur Rev Med Pharmacol Sci. 2020 Aug;24(15):8143-8150. doi: 10.26355/eurrev_202008_22501.
This study evaluated the efficacy of the soluble epoxide hydrolase (sEH) inhibitor, TPPU on chronic NG-Nitro L-arginine methyl ester (L-NAME)-induced hypertension in rats and its effects on plasma Angiotensin II (Ang II), cardiac Angiotensin-converting enzyme (ACE) and Angiotensin II receptor type 1 (AT1R) expressions.
Forty Sprague Dawley rats were divided into 5 groups. Two groups served as control and received orally either vehicle or TPPU (3 mg/kg) for five weeks. The other three groups were given L-NAME (50 mg/kg/day) in drinking water for five weeks. Two weeks after the L-NAME treatment, animals received orally either saline or TPPU (3 mg/kg/day) or lisinopril (10 mg/kg/day) daily for 3 weeks. Blood pressure (BP) was measured weekly. At the end of the experiment, plasma Ang II, cardiac ACE and AT1R protein and gene expressions were determined.
L-NAME caused a significant increase in BP of the animals. TPPU and lisinopril resulted in normalization of L-NAME-induced hypertension. They also caused a significant reduction in Ang II and ACE protein and gene expressions compared to L-NAME and vehicle-treated animals.
This study demonstrates that TPPU effectively lowers L-NAME-induced hypertension in rats. The mechanism of its antihypertensive effect is likely mediated by the suppression of ACE gene and protein expression, leading to a lower Ang II level.
本研究评估了可溶性环氧化物水解酶（sEH）抑制剂 TPPU 在慢性 NG-硝基 L-精氨酸甲酯（L-NAME）诱导的高血压大鼠中的疗效及其对血浆血管紧张素 II（Ang II）、心脏血管紧张素转换酶（ACE）和血管紧张素 II 受体 1（AT1R）表达的影响。
40 只 Sprague Dawley 大鼠分为 5 组。两组作为对照，分别给予 vehicle 或 TPPU（3mg/kg）口服 5 周。其余三组给予 L-NAME（50mg/kg/天）饮用水 5 周。L-NAME 治疗 2 周后，动物每日给予生理盐水或 TPPU（3mg/kg/天）或赖诺普利（10mg/kg/天）口服 3 周。每周测量血压。实验结束时，测定血浆 Ang II、心脏 ACE 和 AT1R 蛋白和基因表达。
L-NAME 导致动物血压显著升高。TPPU 和赖诺普利使 L-NAME 诱导的高血压正常化。与 L-NAME 和 vehicle 处理的动物相比，它们还导致 Ang II 和 ACE 蛋白和基因表达显著降低。
本研究表明 TPPU 可有效降低 L-NAME 诱导的高血压大鼠血压。其降压作用的机制可能是通过抑制 ACE 基因和蛋白表达，导致 Ang II 水平降低。
