Modulating NO–GC Pathway in Pulmonary Arterial Hypertension

Figures

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  Figure 1. NO Synthesis. Metabolic pathway of NO synthesis from arginine by endothelial, neuronal, or inducible isoforms of the enzyme NO synthase with concomitant formation of citrulline.

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  Figure 2. NO effects on the healthy myocardium. NOS–NO signaling effects on cardiovascular function are mediated through direct phosphorylation of myosin-binding protein C (MYBPC) and troponin I (TnI), which are responsible for the reduction in myofilament Ca2+ sensitivity.

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  Figure 3. The NO pathway in cardiac myocytes. A schematic illustration of Ca2+ fluxes during excitation-contraction in ventricular cardiomyocytes. This diagram depicts the most representative protein complexes and intercellular organelles involved in the cardiac excitation-contraction coupling. Efficient systolic contraction and diastolic relaxation is reliant on efficient Ca2+ handling through several processes. Diffusion of Ca2+ into the cytosol through LTCC, L-type Ca2+ channel; Ca2+-induced-Ca2+-release from the ryanodine receptors (RyRs); Sequestration of Ca2+ back in to the sarcoplasmic reticulum via the important Ca2+ pump sarco/endoplasmic reticulum Ca2+ ATPase (SERCA); and Expulsion of Ca2+ from the cell via sodium-calcium exchanger pumps (NCX); PLB, phopholamban; Ca2+, calcium.

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  Figure 4. Mode of action of riociguat and PDE5i. Riociguat acts on the nitric oxide (NO) receptor, soluble guanylate cyclase (sGC), and stimulates the enzyme independently of NO. On the other side, PDE5i bind to the catalytic site of the PDE5 enzyme to act as a competitive inhibitor of cGMP, avoiding its conversion to GMP.