Interaction between endothelin-induced Na+ and Ca2+ kinetics in cultured rat vascular smooth muscle cells

The present study was undertaken to examine the interaction between endothelin-1 (ET-1)-induced Ca2+ and Na+ kinetics in cultured rat vascular smooth muscle cells (VSMCs) by measuring cytosolic free Ca2+ ([Ca2+]i) and intracellular Na+ ([Na+]i) using intracellular fluorescent dyes (fura-2 and SBFI, respectively). ET-1 increased both [Ca2+]i (basal, 58.9 nM; 10(-9) M, 119.8 nM; 10(-8) M, 265.0 nM; 10(-7) M, 419.0 nM) and [Na+]i (basal, 13.4 mM; 10(-9) M, 17.1 mM; 10(-8) M, 21.6 mM; 10(-7) M, 25.2 mM) in a dose-dependent manner in cultured rat VSMCs. The Na(+)-free solution enhanced the 10(-7) M ET-1-mobilized [Ca2+]i (419 vs. 1,192 nM) but reduced the 10(-7) M ET-1-induced increase in [Na+]i (25.2 vs. 6.1 mM). The Ca(2+)-free solution decreased the peak levels of 10(-7) M ET-1-induced mobilization of [Ca2+]i (411 vs. 350 nM) and the sustained increase in [Ca2+]i and totally diminished the 10(-7) M ET-1-induced increase in [Na+]i (25.2 vs. 12.8 mM). These results therefore indicate that ET-1 increases [Na+]i in association with an increase in cellular Na+ and Ca2+ uptake in VSMCs.