It is well established that angiotensin II (AII) rapidly increases free cytosolic Ca2+ in vascular smooth muscle cells (VSMCs). Several studies have indicated that the hormone also plays a role in Na+-K+ regulation of these cells. In this study, we explored the mechanism of AII effect on 22Na+ transport in cultured rat VSMCs. The 22Na+ washout from these cells was described by three exponents with exponential factors k1 greater than k2 greater than k3. In 1.8 mM Ca2+ medium, AII (10(-9)-10(-6) M) increased (in a dose response manner) the k1 value, and consequently the initial washout rate constant (kei) for the isotope. AII had no effect on kei in Ca2+-deficient medium or in the presence of ouabain. Amiloride (10(-3) M) and verapamil (10(-5) M) abolished the AII induced increase in kei. These findings are consistent with angiotensin II stimulation of an amiloride-sensitive Na+ transport, which is likely to represent the Na+/H+ antiport. In cultured VSMCs, the sustained stimulation by AII of this transport system requires the presence of extracellular Ca2+ and its influx into these cells.