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

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 1n20 mg/kg i.v. produced hypotension and dose-dependent bradycardia. In mesenteric rings pre-contracted with phenyle- phrine (PHE) (10 -5 M), AMQ caused concentration-dependent relaxation (IC50 = (1.34 ± 0.04) ◊ 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, vasore- laxation 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 Ca 2+ -activated K + (BKCa) and KATP channels, respectively. Additionally, AMQ reduced CaCl2-induced contractions in Ca 2+ -free solution containing KCl, probably due to its non-selective opening of K + channels or may be acting as Ca 2+ -antagonist. Furthermore, AMQ did not interfere with Ca 2+ 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 extra- cellular Ca 2+ influx.