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 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.
Adaramoye
Oluwatosin A
OA
Drug Metabolism and Toxicology Unit, Department of Biochemistry, University of Ibadan, Nigeria. aoadaramoye@yahoo.com
Almeida
Monica M
MM
D000655:Amodiaquine / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
D000962:Antimalarials; D015221:Potassium Channels; D000655:Amodiaquine; D002118:Calcium