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.