Topics on the Na+/Ca2+ exchanger: involvement of Na+/Ca2+ exchanger in the vasodilator-induced vasorelaxation

Many kinds of vasodilators induce relaxation of the vascular smooth muscle cells (VSMCs) through the production of cyclic AMP (cAMP) or cyclic GMP (cGMP). The relaxant effects mediated by these second messengers are thought to be mainly due to the decrease in intracellular Ca(2+) concentration ([Ca(2+)](i)), as well as the decrease in Ca(2+) sensitivity of the contractile apparatus of VSMCs. To explain the cAMP- or cGMP-mediated decrease in [Ca(2+)](i), several mechanisms have been proposed, including the inhibition of Ca(2+) influx due to a hyperpolarization, a stimulation of Ca(2+) uptake into the intracellular store, and an increase in Ca(2+) extrusion from VSMCs by stimulation of sarcolemmal Ca(2+)-pump. VSMCs have two major systems for Ca(2+) extrusion, namely, sarcolemmal Ca(2+)-pump and Na(+)/Ca(2+) exchanger (NCX). However, the involvement of NCX in the vasodilator-induced relaxation of VSMCs has not been well established. In this article, the possible involvement of NCX in the vasodilator-induced relaxation of VSMCs will be reviewed.