Fig. 7

NO/cGMP pathway in cardiomyocytes. NO in the body is produced from L-arginine as a raw material, which is transported into the cell via the cell membrane arginine transporter, and is produced under the action of NOS. The production of NO then activates soluble guanylate cyclase and catalyses the formation of cGMP. The formed cGMP activates PKG. Phosphodiesterase 5 is responsible for the decomposition of cGMP produced by soluble guanylate cyclase, while Phosphodiesterase 9 is responsible for the decomposition of cGMP produced by pGC. The drug stimulates the production of a second messenger cAMP via a Gs-coupled β-adrenergic receptor. cAMP activates PKA, and PKA thenactivates K + channels also increases hyperpolarization, thus indirectly preventing extracellular Ca2 + influx and promoting vasodilation. Abbreviations: cGMP:Cyclic guanosine monophosphate; eNOS: Endothelial nitric oxide synthase; NOS: Nitric oxide synthase; PKA: cAMP-dependent protein kinase; PKG: cGMP-dependent protein kinase; 5’GMP:Guanosine 5′-monophosphate; SERCA2a: Sarco/endoplasmic reticulum Ca2 + −ATPase, SR: Sarco/endoplasmicreticulum, RyR2: Ryanodine receptor 2