Na-H exchange is a major pathway for Na influx in rat vascular smooth muscle

Rat aortic segments and aortic smooth muscle cells in primary culture were used to examine the importance of the Na-H exchange system in transporting Na into smooth muscle. Ethylisopropylamiloride was approximately 100 times more potent than amiloride at inhibiting Na influx into smooth muscle. In a 135 mM Na-containing medium approximately 80% of the Na influx rate could be inhibited by 100 microM ethylisopropylamiloride. The rate of Na entry into cells was markedly influenced by extracellular and intracellular pH. Elevating extracellular pH from 6.0 to 8.0 increased the Na influx rate. The dependence of the Na influx rate on intracellular pH was demonstrated by acidification of cells with nigericin or preincubation with ammonium chloride. These two procedures increased 22Na+ influx rate by about 3.5-fold. In both instances the increases in 22Na+ influx rate could be completely attenuated by ethylisopropylamiloride. Increases in Na influx rate via the Na-H exchange also increased the activity of the Na-K pump, thereby maintaining intracellular Na content approximately constant. These results indicate that Na-H exchange is a major influx pathway for Na in rat vascular smooth muscle. Activation of this system activates the Na-K pump, which maintains intracellular Na constant.