![Figure 1. The NO-cGMP pathway. HU acts as a NO donor in vivo and/or directly activates intracellular sGC. NO stimulates intracellular sGC to produce cGMP from guanosine-5′-triphosphate. Stimulation of cGMP-dependent protein kinase (PKG) by cGMP in erythroid lineage cells elevates HBG and fetal hemoglobin production and decreases leukocyte (WBC) adhesive mechanisms. PDE9 degrades intracellular cGMP to GMP and is highly expressed in hematopoietic cells. BAY73-6691 is a selective inhibitor of PDE9, and therefore elevates intracellular cGMP in cells that express the enzyme. PTIO is a radical scavenger for nitric oxide. L-NAME is an arginine analog that inhibits nitric oxide synthase activity. ODQ (1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one) is a selective inhibitor of sGC, whereas KT5823 selectively inhibits PKG.](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/120/14/10.1182_blood-2012-02-409524/4/zh89991296200001.jpeg?Expires=1722772076&Signature=OfNK0Kh2MUe~66WoqQeza~jOxB6H8lmOscMMm1M6hnDKvQhFZYSBUPENRi1JPSs9UcyILMAbpqC0~Gw72RWhKU0SSH5xuAyWQ~2RlD03lS4rXYs4L3cTWgoJGE1j3jwuXekIt5BKI9ofz2UYBvXnSLQpEN3UZH8AX2NMNSXgZ6-NfL3CfyjiYjYW0bmF~90f-gj9xunA-20yUE-GDHx0zOsoziIZDkOZP2z5Z3Legsv0KbhUCn76NTxfo7Ga6TQzfeVD3-NAKK7PgOjNdcz8h3YuvT0VwDFKPg1HP8UluHIfrt8GPSBpnGk66Bjf-~GjkV~tzqMewQ9X3NbG80SGZQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
The NO-cGMP pathway. HU acts as a NO donor in vivo and/or directly activates intracellular sGC. NO stimulates intracellular sGC to produce cGMP from guanosine-5′-triphosphate. Stimulation of cGMP-dependent protein kinase (PKG) by cGMP in erythroid lineage cells elevates HBG and fetal hemoglobin production and decreases leukocyte (WBC) adhesive mechanisms. PDE9 degrades intracellular cGMP to GMP and is highly expressed in hematopoietic cells. BAY73-6691 is a selective inhibitor of PDE9, and therefore elevates intracellular cGMP in cells that express the enzyme. PTIO is a radical scavenger for nitric oxide. L-NAME is an arginine analog that inhibits nitric oxide synthase activity. ODQ (1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one) is a selective inhibitor of sGC, whereas KT5823 selectively inhibits PKG.
