Title: 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), a soluble epoxide hydrolase inhibitor, lowers L-NAME-induced hypertension through suppression of angiotensin-converting enzyme in rats.
Authors: Bukhari, I A; Alorainey, B I; Al-Motrefi, A A; Mahmoud, A; Campbell, W B; Hammock, B D
Published In Eur Rev Med Pharmacol Sci, (2020 08)
Abstract: OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
PubMed ID: 32767352
MeSH Terms: Angiotensin II/metabolism; Angiotensin Receptor Antagonists/pharmacology*; Angiotensin-Converting Enzyme 2/antagonists & inhibitors*; Angiotensin-Converting Enzyme 2/metabolism; Angiotensin-Converting Enzyme Inhibitors/pharmacology*; Animals; Epoxide Hydrolases/antagonists & inhibitors*; Epoxide Hydrolases/metabolism; Hypertension/chemically induced; Hypertension/drug therapy*; Male; NG-Nitroarginine Methyl Ester; Phenylurea Compounds/pharmacology*; Piperidines/pharmacology*; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1/metabolism