Figure 4.

Cardioprotective effects of NO, H₂S, and HNO. There are multiple underlying mechanisms for cardioprotective effect of H₂S. It has been demonstrated to induce K_ATP channel opening, abolish inflammation and oxidative stress by inhibiting ROS production, block LTCC and intracellular cAMP signaling pathway, and inhibit Na⁺/H⁺ exchanger activity. Furthermore, NO also plays an important role in the cardioprotective effect of H₂S. Endogenous NO generated from eNOS in endothelial cells initiates the sGC-cGMP-PKG cascade to increase openings of subcellular (mitochondrial) K_ATP channels. The resultant inhibition of mitochondrial permeability transition (MPT) is responsible for decreased cytochrome C release and apoptosis in cardiomyocytes. HNO, depending on the concentration, can be either cardioprotective or cardiotoxic. At low concentration, just like NO, HNO also stimulates K_ATP channels opening in mitochondria.