Increases in intracellular calcium of arterial smooth muscle cells in transgenic mice overexpressing Na+/H+ exchanger.

We produced transgenic mice overexpressing Na+/ H+ exchanger as a model of salt-sensitive hypertension and reported that dietary salt loading elevates blood pressure in these transgenic mice. We speculate that this blood pressure elevation may be attributed to the elevation of intraarterial smooth muscle Ca2+ concentration through Na+/Ca2+ exchange. To test this hypothesis, we measured the isometric tension of aortic rings and intracellular free calcium ([Ca2+]i) of cultured smooth muscle cells. In the transgenic mice, the aortic ring contraction induced by 5 mM caffeine (percentage of 60 mM K-induced contraction) was significantly greater than control mice (60.1 +/- 5.5% vs. 44.8 +/- 3.1%). The mean [Ca2+]i in vascular smooth muscle cells (VSMCs) of transgenic mice (123.1 +/- 19.7 nM) was higher than those in VSMCs of control mice (66.6 +/- 7.2 nM). These observations suggest that dietary salt loading increases the concentration of calcium in arterial smooth muscle cells in this transgenic mice. These findings are helpful in tracing the causes of salt-sensitive hypertension.