Theoretical investigation of Ca²⁺ dynamics in normal and hypertensive vascular walls

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.