Figure 2.

Summary Hypothesis: Diabetes transforms the “normal” vasodilatory response of CASM to estrogen into coronary vasoconstriction by enhancing ROS production. Because BH₄ and L-arginine levels are depleted by diabetes, there should be greater potential for “uncoupled” NOS to produce mainly superoxide (and peroxynitrite). This increased oxidative stress opens Ca channels and/or closes BK_Ca channels, thus leading to increased [Ca²⁺], and coronary artery contraction.