Nitric oxide (NO) (NO)

Nitric oxide (NO) is a critical gaseous signaling molecule produced by endothelial nitric oxide synthase (eNOS) that regulates vascular tone by activating soluble guanylyl cyclase in smooth muscle cells, leading to vasodilation (Ignarro, 1990). In the context of hemoximer (HBOC-201), a glutaraldehyde-polymerized bovine hemoglobin, the heme iron sites of the acellular hemoglobin molecules act as potent scavengers of endogenous NO (Doherty et al., 1998). This scavenging effect occurs because the heme iron has a high affinity for NO, which is significantly greater than its affinity for oxygen, leading to the rapid sequestration of NO as it diffuses from the endothelium toward the smooth muscle (Olson et al., 2004). The resulting reduction in bioavailable NO causes significant vasoconstriction and systemic hypertension, which are the primary adverse effects associated with the administration of hemoglobin-based oxygen carriers (Natanson et al., 2008). While hemoximer is designed to provide oxygen-carrying capacity in patients where red blood cells are unavailable or contraindicated, its interaction with nitric oxide remains a central challenge in its clinical application and safety profile (Silverman and Weiskopf, 2009).

Other names

Nitrogen monoxideEndothelium-derived relaxing factorEDRF

Hemoximer (HBOC-201) functions as a nitric oxide scavenger; the heme iron sites within the polymerized bovine hemoglobin bind to and inactivate endogenous nitric oxide, thereby preventing its vasodilatory action on vascular smooth muscle (Doherty et al., 1998; Olson et al., 2004).