Hypotensive and antihypertensive potential of 4-[(1-phenyl-1H-pyrazol-4-yl) methyl]1-piperazine carboxylic acid ethyl ester: a piperazine derivative

Abstract

Aims: Clinical complaints on the first-line of cardiovascular medications make continuous search for new drugs a necessity. This study evaluated the cardiovascular effects and mechanism of 4-[(1-phenyl-1H-pyrazol-4-yl)methyl]1-piperazine carboxylic acid ethyl ester (LQFM008).

Main methods: Normotensive male Wistar or spontaneously hypertensive rats (anesthetized or conscious) were used to evaluate the effect of LQFM008 on the mean arterial pressure (MAP), heart rate (HR), arterial blood flow (ABF), arterial vascular conductance (AVC), baroreflex effectiveness index (BI), systolic blood pressure (SBP), diastolic blood pressure (DBP) and vascular function.

Key findings: In anesthetized normotensive rats, LQFM008 (7.3, 14.3 or 28.6 μmol/kg, i.v.) reduced MAP (-21.1±2.7; -23.9±4.7 or -32.4±8.3 mmHg, respectively) and AVC (22%, 32% or 38%) in a dose-dependent manner. LQFM008 elicited a temporal reduction in the SBP and DBP without changes to the BI of conscious normotensive rats. In hypertensive rats, LQFM008 (7.3, 14.3 or 28.6 μmol/kg, i.v.) reduced MAP (-2.3±2.6; -29.3±2.7 or -38.4±2.8 mmHg, respectively) and increased HR (1.6±3.7; 15.4±4.9 or 25.5±6.2 bmp, respectively) in a dose-dependent manner. A week of oral administration of LQFM008 47.7 μmol/kg elicited a temporal reduction in SBP of hypertensive rats. Pretreatments with atropine, WAY-100635 or L-NAME blocked the effect of LQFM008. In addition, LQFM008-induced endothelium-dependent vascular relaxation was inhibited by L-NAME.

Significance: Our findings showed hypotensive, antihypertensive and vasorelaxant effects of LQFM008 and suggest the participation of nitric oxide, 5-HT1A and muscarinic receptors.

Keywords: Aortic rings; LQFM008; Normotensive rat; Spontaneously hypertensive rat.