Faculty Collaboration Database

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

08/09/2020

Pubmed ID

32767352

Pubmed Central ID

PMC7990106

DOI

10.26355/eurrev_202008_22501

Scopus ID

2-s2.0-85089301773 (requires institutional sign-in at Scopus site)   5 Citations

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.

Author List

Bukhari IA, Alorainey BI, Al-Motrefi AA, Mahmoud A, Campbell WB, Hammock BD

Author

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiotensin II
Angiotensin 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