Cation Transport Systems

In addition to influencing signaling pathways associated with cell growth and inflammation, ROS modulate intracellular Ca2+ concentration ([Ca2+].), a major determinant of vascular contraction. Superoxide and H2O2 increase [Ca2+]i in VSMCs and endothelial cells.109 These effects have been attributed to redox-dependent inositol-trisphosphate-induced Ca2+ mobilization, increased Ca2+ influx, and decreased activation of Ca2+-ATPase.109110 Plasma membrane K+ channels in VSMCs that control a hyperpolarization-elicited relaxation are opened by mechanisms associated with thiol oxidation by ROS.99 100 110 These redox-regulated Ca2+ processes may be more important in stress responses than in receptor-mediated signaling by growth factors or cytokines and may play a role in altered vascular contractility in hypertension. In fact contractile responses to H2O2 are exaggerated in arteries from SHR compared with normotensive counterparts,111 suggesting that in addition to impaired endothelium-dependent vasodilation (due to increased quenching of NO by *O2-), redox-sensitive Ca2+ changes could contribute to altered vascular tone in hypertension.

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