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. Eur Rev Med Pharmacol Sci 2020 Aug;24(15):8143-8150
Date
08/09/2020Pubmed ID
32767352Pubmed Central ID
PMC7990106DOI
10.26355/eurrev_202008_22501Scopus ID
2-s2.0-85089301773 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
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.
Author List
Bukhari IA, Alorainey BI, Al-Motrefi AA, Mahmoud A, Campbell WB, Hammock BDAuthor
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiotensin IIAngiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Animals
Epoxide Hydrolases
Hypertension
Male
NG-Nitroarginine Methyl Ester
Phenylurea Compounds
Piperidines
Rats
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1