1. 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.
- Author
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Bukhari, IA, Alorainey, BI, Al-Motrefi, AA, Mahmoud, A, Campbell, WB, and Hammock, BD
- Subjects
Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Hypertension ,Cardiovascular ,Angiotensin II ,Angiotensin Receptor Antagonists ,Angiotensin-Converting Enzyme 2 ,Angiotensin-Converting Enzyme Inhibitors ,Animals ,Epoxide Hydrolases ,Male ,NG-Nitroarginine Methyl Ester ,Phenylurea Compounds ,Piperidines ,Rats ,Rats ,Sprague-Dawley ,Receptor ,Angiotensin ,Type 1 ,Soluble epoxide hydrolase inhibitors ,TPPU ,L-NAME induced hypertension ,Angiotensin converting enzyme ,Angiotensin type 1 receptors ,Gastroenterology & Hepatology ,Pharmacology and pharmaceutical sciences ,Medicinal and biomolecular chemistry - Abstract
ObjectiveThis 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 methodsForty 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.ResultsL-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.ConclusionsThis 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.
- Published
- 2020