Using a theoretical model of smooth muscle cell from rat mesenteric arterioles, we investigated calcium dynamics in normal and hypertensive vascular wall. The model incorporated a detailed description of plasma membrane, cytosol and intracellular stores. Inhibition of Na+-K+ pump (NaK) simulated the effect of ouabain in salt sensitive hypertension. The inhibition caused intracellular sodium accumulation that compromised or reversed Na +-Ca2+ exchanger (NCX) and increased resting [Ca 2+]i and reactivity to norepinephrine (NE). NCX inhibition could compensate the effect of NaK block on the agonist-induced Ca2+ plateau, but it further increased resting Ca2+ and NE-induced Ca2+ transients. These undesirable effects could be avoided by selective inhibition of the reverse mode of NCX. In conclusion, NaK blockade elevated Ca+ levels, in agreement with experimental data, and this effect was reduced by inhibition of NCX reverse mode. The results provide evidence for the beneficial effects of a new class of antihypertensive pharmaceuticals.
