Referenced in: none

Automatically associated channels: BKβ

Title: Vasorelaxation induced by amodiaquine in rat superior mesenteric arteries: in vivo and in vitro studies.

Authors: Oluwatosin A Adaramoye, Monica M Almeida

Journal, date & volume: Acta Pol Pharm, 2010 Sep-Oct , 67, 529-36

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20873422

Abstract
The aim of this study was to investigate the mechanisms underlying vasorelaxation induced by amodiaquine (AMQ) in rat superior mesenteric arteries. In normotensive, conscious rats, AMQ at 1-20 mg/kg i.v. produced hypotension and dose-dependent bradycardia. In mesenteric rings pre-contracted with phenylephrine (PHE) (10(-5) M), AMQ caused concentration-dependent relaxation [IC50 = (1.34 +/- 0.04) x 10(-5) M, Emax = 67.5 +/- 0.8%]. Vasorelaxation induced by AMQ was unaffected after removal of the endothelium (Emax = 66.9 +/- 0.3%, p > 0.05), and in the presence of ouabain (10(-4) M) (Emax = 65.4 +/- 1.9%, p > 0.05). In contrast, vasorelaxation evoked by AMQ was significantly inhibited after pre-treatments with 4-aminopyridine (10(-3) M), tetraethylammonium (10(-3) M) and glibenclamide (10(-5) M), blockers of voltage-dependent K+ (Kv), large and intermediate conductance Ca2+ -activated K+ (BK(Ca)) and K(ATP), channels, respectively. Additionally, AMQ reduced CaCl2-induced contractions in Ca2+ -free solution containing KCl, probably due to its non-selective opening of K+ channels or may be acting as Ca2+ -antagonist. Furthermore, AMQ did not interfere with Ca2+ release from intracellular stores mediated by either phenylephrine (10(-5) M) or caffeine (0.02 M). Collectively, these results provide functional evidence that AMQ-induced hypotensive and bradycardic effects may involve the opening of K+ channels sensitive to 4-aminopyridine, tetraethylammonium and glibenclamide or the blockade of extracellular Ca2+ influx.