FIG. 2.

Cardioprotection role of S-nitrosylation of L-type Ca²⁺ channel in ischemic reperfused heart under adrenergic stimulation. An increase in Ca²⁺ before the ischemia, as occurs under β-adrenergic stimulation or other hypercontractile conditions, causes Ca²⁺ overload and an increased ischemia–reperfusion (I/R) injury (text in black). However, the increased cytosolic Ca²⁺ leads to a greater increase (+) in NO production and protein S-nitrosylation in females, because of increased constitutive NOS (cNOSs), eNOS, and nNOS association with caveolin-3 in females. The increase in S-nitrosylation of the L-type Ca²⁺ channel in females reduces (−) Ca²⁺ entry and SR Ca²⁺ loading at the start of ischemia, thereby reducing Ca²⁺ overload during ischemia and reperfusion and thus reducing ischemia–reperfusion injury (text in grey).