Angiotensin II (Ang II) has an important role in cardiovascular regulation and in the control of electrolyte balance, and its role in the regulation of Na+ transcellular movements through its actions on the activity of Na+/K+ ATPase is well documented. We showed previously that human umbilical vein endothelial cells (HUVEC) express the Ang II type 1 (AT1) receptor, which mediates Ang II modulation of Na+/K+ ATPase activity (1). We here investigate the effects of Ang II on the activity of the Na+/H+ exchanger in HUVEC. When compared with controls, incubation of HUVEC for 20 min with different concentrations of Ang II provoked significant increases in Na+/H+ activity. The stimulation was dose dependent between 1 and 10 nM Ang II and varied with time of incubation up to 20 min. The maximal response, obtained with 10 nM Ang II after 20 min treatment, resulted in a 65% increment in Na+/H+ activity. Preincubation of HUVEC with 10 microM DuP753 blocked Na+/H+ activation by Ang II. These results suggest that the effects of Ang II on both the Na+/K+ ATPase and the Na+/H+ exchanger may increase the transendothelial flux of Na+ and are mediated by the AT1 receptor.