Nitric oxide modulates myocardial G protein-coupled receptor signaling components, including GRK2 and β-arrestins, through S-nitrosylation, impacting cardiac regulation in heart failure.
Cardiac diseases including heart failure (HF), are the leading cause of morbidity and mortality globally. Among the prominent characteristics of HF is the loss of β-adrenoceptor (AR)-mediated inotropic reserve. This is primarily due to the derangements in myocardial regulatory signaling proteins, G protein-coupled receptor (GPCR) kinases (GRKs) and β-arrestins (β-Arr) that modulate β-AR signal termination via receptor desensitization and downregulation. GRK2 and β-Arr2 activities are elevated in the heart after injury/stress and participate in HF through receptor inactivation. These GPCR regulators are modulated profoundly by nitric oxide (NO) produced by NO synthase (NOS) enzymes through S-nitrosylation due to receptor-coupled NO generation. S-nitrosylation, which is NO-mediated modification of protein cysteine residues to generate an S-nitrosothiol (SNO), mediates many effects of NO independently from its canonical guanylyl cyclase/cGMP/protein kinase G signaling. Herein, we review the knowledge on the NO system in the heart and S-nitrosylation-dependent modifications of myocardial GPCR signaling components GRKs and β-Arrs.
Kayki‐Mutlu et al. (Thu,) conducted a review in Heart failure. Nitric oxide and S-nitrosylation was evaluated. Nitric oxide modulates myocardial G protein-coupled receptor signaling components, including GRK2 and β-arrestins, through S-nitrosylation, impacting cardiac regulation in heart failure.