Figure 3. Schematic summary of a hypothetical NO signaling cascade activated by mechanical stretch in cardiomyocytes. Mechanical stretch initiates the NO cascade by activating constitutively expressed eNOS through [Ca²⁺]_i elevation. The active eNOS produces a small amount of NO, which further induces iNOS expression. iNOS, once expressed, produces a larger amount of NO, thus amplifying NO signaling. Finally, NO concentration reaches a certain level that is high enough to induce apoptosis and/or other responses in cardiomyocytes. NO may affect mitochondria or other apoptotic pathways to induce apoptosis. Besides this NO cascade, stretch-induced Ca²⁺ may participate in other signaling pathways. Solid lines indicate signaling discovered in this study. Dashed lines indicate possible signaling.