Topics on the Na⁺/Ca²⁺ Exchanger:
Involvement of Na⁺/Ca²⁺ Exchanger in the Vasodilator-Induced Vasorelaxation

Abstract

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 Ca²⁺ concentration ([Ca²⁺]_i), as well as the decrease in Ca²⁺ sensitivity of the contractile apparatus of VSMCs. To explain the cAMP- or cGMP-mediated decrease in [Ca²⁺]_i, several mechanisms have been proposed, including the inhibition of Ca²⁺ influx due to a hyperpolarization, a stimulation of Ca²⁺ uptake into the intracellular store, and an increase in Ca²⁺ extrusion from VSMCs by stimulation of sarcolemmal Ca²⁺-pump. VSMCs have two major systems for Ca²⁺ extrusion, namely, sarcolemmal Ca²⁺-pump and Na⁺/Ca²⁺ 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.