title: Hypotensive and antihypertensive potential of 4-[(1-phenyl-1H-pyrazol-4-yl) methyl]1-piperazine carboxylic acid ethyl ester: a piperazine derivative.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our findings showed hypotensive, antihypertensive and vasorelaxant effects of LQFM008 and suggest the participation of nitric oxide, 5-HT1A and muscarinic receptors.
authors: Department of Physiological Sciences, Federal University of Goiás, Campus Samambaia, 74001-970 Goiâania, GO, Brazil. Electronic address: rm_rj@yahoo.com.
authors: James Oluwagbamigbe
authors: JO
authors: Fajemiroye
authors: Department of Physiological Sciences, Federal University of Goiás, Campus Samambaia, 74001-970 Goiâania, GO, Brazil.
authors: Nathalia Oda
authors: NO
authors: Amaral
authors: Department of Physiological Sciences, Federal University of Goiás, Campus Samambaia, 74001-970 Goiâania, GO, Brazil.
authors: Elaine Fernanda
authors: EF
authors: da Silva
authors: Department of Physiological Sciences, Federal University of Goiás, Campus Samambaia, 74001-970 Goiâania, GO, Brazil.
authors: Pablinny Morreira
authors: PM
authors: Galdino
authors: Department of Physiological Sciences, Federal University of Goiás, Campus Samambaia, 74001-970 Goiâania, GO, Brazil.
authors: Thiago Sardinha
authors: TS
authors: de Oliveira
authors: Department of Physiological Sciences, Federal University of Goiás, Campus Samambaia, 74001-970 Goiâania, GO, Brazil.
authors: Paulo César
authors: PC
authors: Ghedini
authors: Department of Pharmacognosy and National Center for Natural Product Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS 38677-1848, USA.
authors: Jordan K
authors: JK
authors: Zjawiony
authors: Department of Physiological Sciences, Federal University of Goiás, Campus Samambaia, 74001-970 Goiâania, GO, Brazil.
authors: Elson Alves
authors: EA
authors: Costa
authors: Department of Physiological Sciences, Federal University of Goiás, Campus Samambaia, 74001-970 Goiâania, GO, Brazil.
authors: Gustavo Rodrigues
authors: GR
authors: Pedrino
authors: Pharmacy Faculty, Federal University of Goiás, Setor Universitário, 74000-000, Goiânia, GO, Brazil.
authors: Ricardo
authors: R
authors: Menegatti
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects* / Q000503:physiopathology; D001285:Atropine / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D046509:Tissue Culture Techniques; D014664:Vasodilation / Q000187:drug effects
chemical_list: C574301:4-(1-phenyl-1H-pyrazol-4-ylmethyl)piperazine-1-carboxylic acid ethyl ester; D000959:Antihypertensive Agents; D010879:Piperazines; D011720:Pyrazoles; D011725:Pyridines; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D001285:Atropine; D019331:NG-Nitroarginine Methyl Ester
keywords: Aortic rings; LQFM008; Normotensive rat; Spontaneously hypertensive rat