Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Vasodilator effect of 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea is predominantly mediated through activation of voltage-dependent K+ channels

Shafiq Ali Shah^1,2, Malik Hassan Mehmood^1,3 , Munasib Khan², Ishfaq Ali Bukhari⁴, Anwarul Hassan Gilani¹

¹Natural Product Research Division, Department of Biological and Biomedical Sciences, Aga Khan University, Karachi; ²Department of Pharmacy, University of Malakand, KPK; ³Department of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan; ⁴Department of Pharmacology College of Medicine, King Saud University, Riyadh, Saudi Arabia.

For correspondence:- Malik Mehmood Email: malikhassan.mehmood@gmail.com

Accepted: 13 May 2018 Published: 30 June 2018

Citation: Shah SA, Mehmood MH, Khan M, Bukhari IA, Gilani AH. Vasodilator effect of 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea is predominantly mediated through activation of voltage-dependent K+ channels. Trop J Pharm Res 2018; 17(6):1019-1024 doi: 10.4314/tjpr.v17i6.6

© 2018 The authors.
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Abstract

Purpose: To determine the mechanism of vasorelaxant effect of 1-trifluoromethoxyphenyl – 3 -(1-propionylpiperidin–4-yl) urea (TPPU) in cardiovascular diseases, including hypertension.

Methods: Isolated rat thoracic aortic tissue preparations were mounted in an organ bath set up integrated with isometric transducer and a Power Lab assembly. TPPU (0.3 - 100 µM) was tested for vasorelaxant effect against low K⁺ (25 mM) and high K⁺ (80 mM)-induced contractions and its mechanism was determined in the presence of different antagonists (glibenclamide, 4- aminopyridine and tetraethyl ammonium).

Results: In rat aortic preparations, TPPU showed a concentration-dependent (0.3 – 100 µM) and significant (p < 0.001) inhibition of low K⁺ induced contractions with complete inhibition obtained at 100 µM. TPPU produced significant (p < 0.05) inhibition of high K⁺ induced contractions with maximum relaxation of 15.36 ± 1.95 % and 15.85 ± 3.35 % at 30 and 100 µM, respectively. Glibenclamide (Gb,10 µM) pretreatment partially inhibited the vasorelaxant effect of TPPU against low K⁺ in a concentration range of 1 - 30 µM. 4-Aminopyridine (4-AP, 1 mM) and tetraethyl ammonium (TEA, 10 mM), markedly inhibited the vasorelexant effect of TPPU against low K⁺ induced contractions with maximum relaxation of 20.09 ± 2.40 and 21.67 ± 0.88 %, respectively, at 100 µM.

Conclusion: TPPU possesses marked vasorelaxant properties which provides sound pharmacological evidence for its use as a potential drug candidate in the management of hypertension.

Keywords: 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea, Hypertension, vasodilator, K+- channel activation, Ca+- channel antagonist