title: Involvement of Na(+)-Ca (2+) exchanger in the endothelium-independent vasorelaxation induced by Curcuma longa L. in isolated rat superior mesenteric arteries.
abstract: Previous studies confirmed that the methanolic extract from Curcuma longa L. (CLME) lowers arterial blood pressure and heart rate in rats due to the blockade of extracellular Ca(2+) influx. The aim of this study was to investigate the involvement of Na(+)-Ca (2+) exchanger in the vasorelaxant effects elicited by CLME in isolated rat superior mesenteric arteries. CLME (1-1,000 microg/ml) concentration-dependently relaxed phenylephrine (PHE) (10 microM) pre-contracted arterial rings with intact-endothelium (pD(2) and E(max) = 2.04 +/- 0.06 and 88.3 +/- 3.2%) or denuded-endothelium (pD(2) and E(max) = 2.06 +/- 0.03 and 91.4 +/- 1.0%), respectively, suggesting that the removal of endothelium has no significant effect (P>0.05) on the vasorelaxation induced by CLME. Furthermore, CLME (30, 100 and 300 microg/ml) inhibited the cumulative concentration-response curves to PHE (10(-8)-10(-5) M) in a concentration-dependent manner, whereas, treatment with ouabain 100 microM (selective blocker of Na(+)-K(+) ATPase) has no effect on the relaxant responses of CLME. However, treatment with nickel chloride (NiCl(2)) (100, 300 and 400 microM), a putative Na(+)-Ca(2+) exchanger inhibitor, concentration-dependently reduced the vasorelaxant responses of CLME. Precisely, NiCl(2) at 100, 300 and 400 microM significantly (P<0.05) decreased the pD(2) and E(max) values of CLME (1.86 +/- 0.03 and 81.3 +/- 1.2%, 1.77 +/- 0.03 and 60.2 +/- 0.8%, 1.69 +/- 0.04 and 55.3 +/- 1.6%, respectively). Also, CLME (100 microg/ml) produced less relaxant effect with decreasing extracellular Na(+) concentration. CLME-induced vasorelaxation was completely abolished in a Na(+)-free Tyrode's solution, a condition that eliminates the influence of the forward mode of the exchanger. The results provide indirect evidence that the stimulation of the forward mode of Na(+)-Ca (2+) exchanger may probably contribute to the vasorelaxation induced by CLME in endothelium-denuded arterial rings.
authors.affiliation: Drug Metabolism and Toxicology Unit, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria. aoadaramoye@yahoo.com
authors.forename: Oluwatosin A
authors.initials: OA
authors.lastname: Adaramoye
authors.forename: Isac A
authors.initials: IA
authors.lastname: Medeiros
mesh_terms: D000818:Animals; D030024:Curcuma; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects* / Q000502:physiology*; D009532:Nickel / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D010936:Plant Extracts; D019831:Sodium-Calcium Exchanger; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D010042:Ouabain; C022838:nickel chloride; D009532:Nickel; D000254:Sodium-Potassium-Exchanging ATPase